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Harvard College 
Library 




FROM THE BEQUEST OP 

GEORGE HAYWARD, M.D. 

OF BOSTON. MASSACHUSETTS 



CLASS OF 1M9 



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REGENERATION 



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Columbia SSntbetsitg ]3uiUigtcal Series. 

EDITED BY 
HENRY FAIRFIELD OSBORN 

AND 

EDMUND B. WILSON. 

1. FROM THE CREEKS TO DARWIN. 

By Henry Fairfield Osborn. Sc.D. Princeton. 

2. AMPHIOXUS AND THE ANCESTRY OF THE VERTEBRATES. 

By Arthur Willey. B.Sc. London Univ. 

3. FISHES. LIVINC AND FOSSIL. An Introductory Study. 

By Bashford Dean, Ph.D. Columbia. 

4. THE CELL IN DEVELOPMENT AND INHERITANCE. 

By Edmund B. Wilson, Ph.D. J.H.U. 

5. THE FOUNDATIONS OF ZOOLOGY. 

By William Keith Brooks. Ph.D. Hanr., LL.D. Williams. 

6. THE PROTOZOA. 

By Gary N. Calkins, Ph.D. Columbia. 

7. REGENERATION. 

By Thomas Hunt Morg^an, Ph.D. 



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COLUMBIA UNIVERSITY BIOLOGICAL SERIES. VIL 



REGENERATION 



BY 



THOMAS HUNT MORGAN, Ph.D. 

PROFESSOR OF BIOLOGY, BRYN MAWR COLLEGE 




THE MACMILLAN COMPANY 

LONDON: MACMILLAN & CO., LTD. 
I9OI 

All rights r*s*rvtd 



2 



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^ MOV • 1921^ 



Copyright, 1901, 
By the MACMILLAN COMPANY. 



Noriuood Press 

J, S Cusbing &Co. — Berwick & Smith 

Norwood, Mass.f U.S.A. 



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PREFACE 

This volume is the outcome of a course of five lectures on 
"Regeneration and Experimental Embryology," given in Columbia 
University in January, 1900. The subjects dealt with in the lectures 
are here more fully treated and are supplemented by the discussion 
of a number of related topics. During the last few years the prob- 
lems connected with the regeneration of organisms have interested 
a large number of biologists, and much new work has been done in 
this field ; especially in connection with the regenerative phenomena 
of the egg and early embryo. The development of isolated cells or 
blastomeres has, for instance, aroused widespread interest. It has 
become clearer, as new discoveries have been made, that the latter 
phenomena are only special cases of the general phenomena of 
regeneration in organisms, so that the results have been treated 
from this point of view in the present volume. 

If it should appear that at times I have gone out of my way to 
attack the hypothesis of preformed nuclear germs, and also the 
theory of natural selection as applied to regeneration, I trust that 
the importance of the questions involved may be an excuse for the 
criticism. 

If I may be pardoned a further word of personal import, I should 
like to add that it has seemed to me that far more essential than each 
special question with which the biologist has to deal is his attitude 
toward the general subject of biology as a science. Never before in 
the history of biology has this been more important than at the 
present time, when we so often fail to realize which problems are 
really scientific and which methods are legitimate for the solution 
of these problems. The custom of indulging in exaggerated and 

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viii PREFACE 



unverifiable speculation bids fair to dull our appreciation for hypoth- 
eses whose chief value lies in the possibility of their verification; 
but those who have spent their time and their imagination in such 
speculations cannot hope for long to hold their own against the 
slow but certain advance of a scientific spirit of investigation of 
organic phenomena^ The historical questions with which so many 
problems seem to be connected, and for which there is no rigorous 
experimental test, are perhaps responsible for the loose way in which 
many problems in biology are treated, where fancy too often supplies 
the place of demonstration. If, then, I have tried to use my mate- 
rial in such a way as to turn the evidence against some of the 
uncritical hypotheses of biology, I trust that the book may have 
a wider bearing than simply as a treatment of the problems of 
regeneration. 

I wish to acknowledge my many obligations to Professor H. F. 
Osborn and to Professor E. B. Wilson for friendly criticism and 
advice ; and in connection with the revision of the text I am greatly 
indebted to Professor J. W. Warren, to Professor W. M. Wheeler, 
to Professor G. H. Parker, and to Professor Leo Loeb. 

Bryn Mawr College, Pennsylvania* 
June II, i9oz« 



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CONTENTS 

CHAPTER I 
General Introduction 

PAGB 

Historical Account of the Work on Regeneration of Trembley, Bonnet, and 

Spallanzani i 

Some Further Examples of Regeneration 6 

Definition of Terms 19 

CHAPTER II 

The External Factors of Regeneration in Animals 

The Effect of Temperature 26 

The Effect of Food 27 

The Effect of Light 29 

The Effect of Gravity 30 

The Effect of Contact 33 

The Effect of Chemical Changes in the Environment 35 

General Conclusions 36 

CHAPTER III 

The Internal Factors of Regeneration in Animals 

Polarity and Heteromorphosis 38 

Lateral Regeneration 43 

Regeneration from an Oblique Surface 44 

The Influence of Internal Organs at the Cut-surface 52 

The Influence of the Amount of New Material 54 

The Influence of the Old Parts on the New 62 

The Influence of the Nucleus on Regeneration 65 

The Closing in of Cut-edges 69 



IX 



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X CONTENTS 

CHAPTER IV 
Regeneration in Plants 

PACK 

Regeneration in Flowering Plants 71 

Regeneration in Liverworts, Mosses, and Moulds 84 

Hypothesis of Formative Stufis 88 

CHAPTER V 

Regeneration and Liability to Injury 

Examples of Supposed Connection between Regeneration and Liability to 

Injury 92 

Regeneration in Different Parts of the Body ^^ 

Regeneration throughout the Animal Kingdom 40^ 

Regeneration and the Theory of Natural Selection 108 

CHAPTER vi^ 

Regeneration of Internal Organs. Hypertrophy. Atrophy 

Regeneration of Liver, Eye, Kidney, Salivary Glands, Bones, Muscles, Nerves, 

Brain, and Cord of Vertebrates (^ui 

Examples of Hypertrophy 115 

Theories of Hypertrophy 118 

Atrophy 123 

Incomplete Regeneration 125 

I CHAPTER VII' 
Physiological Regeneration 

Supposed Relation between Physiological Regeneration and Restorative 

Regeneration 128 

Regeneration and Growth 131 

Double Structures 135 

CHAPTER VIII 

Self-division and Regeneration. Budding and Regeneration. 
AuTOTOMY. Theories of Autotomy 

Review of Groups in which Self-division occurs 142 

Division in Plane of Least Resistance 144 



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CONTENTS XI 

PAGB 

Review of Groups in which Budding occurs. Relation of Budding to 

Regeneration 149 

Autotomy 150 

Theories of Autotomy 155 

CHAPTER 4X^ 
Grafting and Regeneration 

Examples of Grafting in Hydra, Tubularia, Planarians, Earthworms, Tadpoles . 159 

Grafting Pieces of Organs in Other Parts of the Body in Higher Animals . (i2§/ 

Grafting of Parts of Embryos of the Frog 182 

Union of Two Eggs to form One Embryo 188 

CHAPTER X^ 
The Origin of New Cells and Tissues 

Origin of New Cells in Annelids 190 

Origin of the New Lens in the Eye of Salamanders 203 

The Part played by the "Germ-layers" in Regeneration .... 207 
The Supposed Repetition of Phylogenetic and Ontogenetic Processes in 

Regeneration 212 

CHAPTER XI^ 
Regeneration in Egg and embryo 

Introduction 216 

Regeneration in Egg of Frog 217 

Regeneration in Egg of Sea-urchin 228 

Regeneration in Other Forms: Amphioxus, Ascidian, Ctenophore, Snail, 

Jelly-fish, Fish 236 

CHAPTER XII 
Theories of Development 

Theories of Isotropy and of Totipotence of Cells 242 

Theory of Qualitative Division of Nucleus 243 

Theory of Equivalency of Cells 244 

Theory of the Organized Structure of the Protoplasm 246 

Theory of Cells as Units 250 



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xii CONTENTS 

PAGE 

Further Analysis of Theories of Qualitative Nuclear Divisions and of the 

Equivalency of Blastomeres 252 

Driesch's Analytical Theory, Criticism, and Later Theories of Driesch . ,253 

Conclusions 256 

CHAPTER XIII 

Theories of Regeneration 

Pre-formation Theory 260 

Comparison with Growth of Crystal • . . • • • • . 263 

Completing Theory » . . 264 

Theory of Formative Stuflfs 265 

Conclusions 269 

Theory of Tensions controlling Growth 271 

CHAPTER XIV 

General Considerations and Conclusions 

Organization 277 

Machine Theory of Development and of Regeneration .... 283 

Teleology 283 

"Action at a Distance" 284 

Definition of Terms : Cause, Stimulus, Factor, Force, Formative Force, 

Organization 287 

Regeneration as a Phenomenon of Adaptation 288 

Literature 293 

Index 311 



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REGENERATION 



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CHAPTER I 
GENERAL INTRODUCTION 

Although a few cases of regeneration were spoken of by Aris- 
totle and by Pliny, the subject first attracted general attention 
through the remarkable observations and experiments of the Abbd 
Trembley. His interest was drawn to certain fresh-water polyps, 
hydras, that were new to him, and in order to find out if the organisms 
were plants ox animals he tried the effect of cutting them into pieces ; 
for it was generally known that pieces of a plant made a new plant, 
but if an animal were cut into pieces, the pieces died. Trembley found 
that the polyp, if cut in two, produced two polyps. Logically, he 
should have concluded that the new form was a plant; but from 
other observations, as to its method of feeding and of movement, 
Trembley concluded that the polyp was an animal, and that the 
property of developing a new organism from a part must belong to 
animals as well as to plants. ** I felt,'* he says, " strongly that nature 
is too vast, and too little known, for us to decide without temerity 
that this or that property is not found in one or another class of 
organized bodies." 

Trembley *s first experiments were made in 1740, and the remark- 
able results were communicated by letter to several other naturalists. 
It came about in this way that before Trembley's memoir had 
appeared, in 1744, his results were generally known, and several 
other observers had repeated his experiments, and extended them 
to other forms, and had even published an account of their own 
experiments, recognizing Trembley, however, as the first discoverer. 
Thus Reaumur described, in 1742, a number of other forms in which 
regeneration takes place; and Bonnet, in 174S, also described some 
experiments that he had made during the four preceding years. 
Widespread interest was aroused by these results, and many different 
kinds of animals were experimented with to test their power of 
regeneration. Most important of these new discoveries were those 
of Spallanzani, who published a short preliminary statement of his 
results, in 1768, in his Prodronto, 

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2 REGENERATION 

Trembley found that when a hydra is cut in two, the time required 
for the development of the new individuals is less during warm than 
during cold weather. He also found that if a hydra is cut into three 
or four parts, each part produces a new individual. If these new 
hydras are fed until they grow to full size, and are then again cut 
into pieces, each piece will produce a new polyp. The new animals 
were kept in some cases for two years, and behaved in all respects 
as do ordinary polyps. 

Trembley also found that if the anterior, or head-end, with its 
tentacles, is cut off, it also will make a new animal. If a hydra is 
cut lengthwise into two parts, the edges roll in and meet, and in an 
hour, or less, the characteristic form may be again assumed. New 
arms may appear later on the new individual. If a hydra is split 
lengthwise into four pieces, each piece will also produce a new polyp. 

If the head-end only of a hydra is split in two, each half becomes 
a new head, and a two-headed hydra results. If each of the new 
heads is split again, a four-headed hydra is produced ; and if each 
of the four heads is once more split in two, an eight-headed hydra is 
formed. A hydra of this kind, in which seven heads had been pro- 
duced in this way, is shown in Fig. \^ A, Each head behaves as a 
separate individual, and all remain united on the same stalk. If the 
foot-end of a hydra is split, a form with two feet is produced. 

One of the most ingenious and most famous experiments that 
Trembley made consisted in turning a hydra inside out (Fig. i, iff, i 
and 2). The animal tends to turn itself back again, but by sticking a 
fine bristle through the body, Trembley thought that the turning back 
could be prevented, and that the inner surface of the hollow body 
remained on the outside, and the outer surface of the body came to 
line the new central cavity. Each layer then changed, he thought, 
its original characteristics, and became like that of the other layer. 
The details of these experiments will be described in a future chapter, 
as well as more recent experiments that have put the results in quite 
a different light. 

Reaumur repeated Trembley's experiment of cutting a hydra into 
pieces, and obtained the same results. He found also that certain 
fresh-water worms, as well as the terrestrial earthworm, regeneratedv 
when cut into pieces. At his instigation two other naturalists^ 
examined the starfish and some marine polyps, and they concluded 
that it was highly probable that these forms also could regenerate. 
Reaumur pointed out that regeneration is more likely to occur in 
fragile forms which are more exposed to injury. 

Bonnet's experiments were made on several kinds of fresh-water 

^ Guettard and Gerard de Villars. Bernard de Jussieu also, who demonstrated that star- 
fish can regenerate. 

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GENERAL INTRODUCTION 



worms, one of which, at least, seems to have been the annelid lum- 
briculus. His first experiments (1741) showed that when the worm 
is cut in two pieces, a new tail develops at the posterior end of the 
anterior piece, and a new head at the anterior end of the posterior 



B 




Fig. I.— ^--ff. AfterTrembley. C-C. After Bonnet. ^, Seven-headed hydra made by splitting 
head-ends lengthwise, a. Illustrating the method of turning hydra inside out by means of 
a bristle : i, foot being pushed through mouth ; a, completion of process. C Middle piece 
of an earthworm (cut into three pieces) with new head and tail. D, Anterior part of an 
earthworm regenerating a new " delicate" tail. E, Posterior third of a worm (lumbriculus) 
that regenerated two heads. F. Middle piece of a worm (another species) cut into three 
pieces. It made a tail at each end. F. Anterior, enlarged end (tail) of last. G, Small 
piece of a worm. G\ Regeneration of head and tail of same. 

piece. He found that if a worm is cut into three, four, eight, ten, 
or even fourteen pieces, each piece produces a new worm ; a new 
head appearing on the anterior end of each piece, and a new tail on 
the posterior end (Fig. i, G, G'). The growth of the new head is 
limited in all cases to the formation of a few segments, but the new 



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4 REGENERATION 

tail continues to grow longer, new segments being intercalated just 
in front of the end-piece that contains the anal opening. In summer 
the regeneration of a new part takes place in two to three days ; in 
winter in ten to twelve days, this difference not being due to the time 
of year, but to the temperature. Bonnet found that if a newly 
regenerated head is cut off, a new one regenerates, and if the second 
one is removed, a third, new one develops, and in one case this oc- 
curred eight times : the ninth time only a bud-like outgrowth was 
formed. In other cases a new head was produced a few more times, 
but never more than twelve. He thought that the capacity of a part 
to regenerate is in proportion to the numb^ of times that the animal 
is liable to be injured under natural conditions. 

Bonnet found that short pieces from the anterior or posterior end 
of the body failed to regenerate, and usually died in a few days. 
Occasionally two new heads appeared at the anterior end of a piece 
(Fig. I, E\ and sometimes two tails at the posterior end. 

Another kind of fresh-water worm ^ was found that gave a very 
remarkable result. If it was cut in two pieces, the posterior piece 
produced at its anterior end, not a new head, but a new tail. Thus 
there is formed a worm with two tails turned in opposite directions, 
as shown in Fig. i, F, F\ 

Spallanzani made many experiments on a number of different 
animals, but unfortunately the complete account of his work was 
never published, and we have only the abstract given in his Prodronto 
(1768). He made a large number of experiments with earthworms 
of several kinds, and found that a worm cut in two pieces may pro- 
duce two new worms ; or, at least, that the anterior piece produces a 
new tail, which increases in length and may ultimately represent the 
posterior part of the body ; the posterior piece, however, produces 
only a short head at its anterior end, but never makes good the rest 
of the part that was lost. A short piece of the anterior end fails to 
regenerate; but in one species of earthworm, that differs from all 
the others in this respect, a short anterior piece or head can make a 
new tail at its posterior end.^ Spallanzani also found that if much of 
the anterior end is cut off, the development of a new head by the 
posterior piece is delayed, and, in some species, does not take place 
at all. 

If a new head is cut off, another is regenerated, and this occurred, 
in one case, five times. If, after a new head has developed, a por- 
tion only is cut off, the part removed is replaced, and if a portion of 
this new part is cut off it is also regenerated. If a worm is split 

^ An annelid of unknown species. 

* This statement of Spallanzani's I interpreted incorrectly ('9^), thinking that he obtained 
a two-tailed form as had Bonnet. 



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GENERAL INTRODUCTION 5 

longitudinally into two pieces, the pieces die. If only a part of the 
worm is split longitudinally and one part removed, the latter will be 
regenerated from the remaining part.^ Several contemporaries of 
Spallanzani also made experiments on the earthworm.^ 

Spallanzani found that a tadpole can regenerate its tail ; and if a 
part of the new tail is cut off, the remaining part will regenerate 
as much as is lost. Older tadpoles regenerate more slowly than 
younger ones. If a tadpole is not fed, it ceases to grow larger, 
but it will still regenerate its tail if the tail is cut off.^ Salamanders 
also regenerate a new tail, producing even new vertebrae. If a leg 
is cut off, it is regenerated; if all four legs are cut off, either at 
the same time or in succession, they are renewed. If the leg is 
cut off near the body, an imperfectly regenerated part is formed. 
Regeneration of the legs was found to take place in all species of 
salamanders that were known to Spallanzani, but best in young 
stages. In full-grown salamanders, regeneration takes place more 
promptly in smaller species than in larger ones. Curiously enough, 
it was found that if the fingers or toes are cut off, they regenerate 
very slowly. If the fingers of one side and the whole leg of the 
opposite side are cut off at the same time, the leg may be regen- 
erated as soon as are the fingers of the other side. A year is, how- 
ever, often insufficient in some forms for a leg to become fully 
formed. If an animal is kept without food for two months after 
a leg has been cut off, the new leg will regenerate as rapidly as in 
another salamander that has been fed during this time. If tne 
animal is kept longer without food, it will decrease in size, but 
nevertheless the new leg continues to grow larger. Occasionally 
more toes or fewer toes than the normal number are regenerated ; 
but as a rule the fore leg renews its four toes, and the hind leg 
its five toes. 

In one experiment, all four legs and the tail were cut off six tines 
during the three summer months, and were regenerated. SpalFan- 
zani calculated that 647 new bones must have been made in the new 
parts. The regeneration of the new limbs was as quickly carried out 
the last time as the first. Spallanzani also found that the upper and 
lower jaws of salamanders can regenerate. 

If the tentacles of a snail or of a slug are cut off, they are renewed ; 
and Spallanzani found that even if the entire head is cut off a new 
one is regenerated. Also other parts of the snail, as the foot, or the 

^ There is some doubt in regard to this statement of Spallanzani's. In a letter to Bonnet 
he denies that this takes place in the earthworm. 

^ Spallanzani refers to the work of Ginnani, Vandelli, Vallisneri, 

' He found that the legs of the tadpole of the frog, and of two species of toads, also have 
the power of regeneration. 



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6 RE GENERA TION 

collar, may be regenerated. The head of the slug, it was found, 
regenerates with more difficulty than does that of the snail. 

These justly celebrated experimentsof Trembley, Reaumur, Bonnet, 
and Spallanzani furnished the basis of all later work. Many new facts, 
it is true, have been discovered, and in many cases we have penetrated 
further into the conditions that influence the regeneration, but many 
of the important facts in regard to regeneration were made known by 
the work of these four naturalists. 



SOME FURTHER EXAMPLES OF REGENERATION 

So many different phenomena are included at the present time 
under the term " regeneration," that it is necessary, in order to get a 
general idea of the subject, to pass in review some typical examples 
of the process. 

The regeneration of different parts of the salamander shows some 
characteristic methods of renewal of lost parts. If the foot is cut ofT 
a new foot is regenerated; if more than the foot is cut off, as much is 
renewed as was lost. For instance, if the cut is made through the 
fore leg, as much of the fore leg as was removed, and also the foot, 
are regenerated; if the cut is made through the upper part of the 
leg, the rest of that part of the leg and the fore leg and the foot are 
regenerated. The new part is at first smaller than the part removed, 
although it may contain all the elements characteristic of the leg. It 
gradually increases in size until it has grown to the same size as the 
leg on the other side of the body, and then its growth comes to an 
end. 

Other parts of the body of the salamander also have the power of 
regeneration. If a part of the tail is cut off, as much is renewed as 
has been removed ; if a part of the lower or upper jaw is cut off, the 
missing part is regenerated ; if a part of the eye is removed, a new eye 
is formed from the part that remains ; but if the whole eye is extir- 
pated, or the whole limb, together with the shoulder girdle, is removed, 
neither structure is regenerated. 

In other vertebrates the power of regeneration is more limited. 
A lizard can regenerate its tail, but not its limbs. A dog can regen- 
erate neither its limbs nor its tail. 

It has been stated that the new limb of the salamander is at first 
smaller than the one removed, but it may contain all the elements of 
the original limb. We find this same phenomenon in other forms, 
and since it is a point of some theoretical interest, a few other 
examples may be given. If the tail of a fish that has a bilobed form 
is cut off near the base, as indicated in Fig. 40, G, there appears '^ver 
the exposed edge a narrow band of new material. Th^ new rt 

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GENERAL INTRODUCTION 7 

now begins to grow faster at two places than at intermediate points, 
as shown in Fig. 40, H, The new tail, although very short, assumes, 
as a result, the characteristic bilobed form. The point of special 



I 



B 




1 1 k 



Fig. 2. — A. AUolobophora faetida. Nonnal worm. B-F. Anterior ends of worms, which, after the 
removal of one, two, three, four, and five segments, have regenerated the same number. 
G, Anterior third cut off. Only five head-segments regenerated. //. Worm cut in two in 
middle. A head-end of five segments regenerated. /. Worm cut in two posterior to middle. 
A heteromorphic tail regenerated at anterior end. 

interest is that the new material that appears over the exposed edge 
does not first grow out at an equal rate at all points until it reaches 
the level of the original fork, and then continue to grow f aster4n twoj 

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8 



REGENERATION 



regions to form the lobes of the tail, but the two regions of most rapid 
growth are very soon established in the new tail. Subsequent growth 
in all parts of the new tail enlarges it to the full size. 




I 



B 






E=I 




/ 



Fig. 3. — A, B. Short head-ends of A.fatida that did not regenerate at posterior surface. C, A 
E. Longer anterior pieces, that made new segments at their posterior ends. F. After Hazen. 
A piece consisting of five (3 to 7) anterior segments grafted, in a reversed position, upon the 
anterior end of another worm. A hetcromorphic head of about two segments regenerated 
at the free end, which is the posterior end of the piece. 

In some cases of regeneration, in which the new part is at first 
smaller than the part removed, the new part represents at first only 
the distal portion of the body, and although the new part may grow 
to the full size, the whole of the part removed may never come back. 

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GENERAL INTRODUCTION 9 . 

This is illustrated in the regeneration of the anterior end of the earth- 
worm ; for example, in the red-banded earthworm, or brandling {Alio- 
lobophora foetidd)} If one segment of the anterior end is cut off, one 
segment is very quickly regenerated (Fig. 2, B)\ if two segments are cut 
off, two come back (Fig. 2, C) ; if three segments are cut off, as many 
are regenerated (Fig. 2, Z?) ; if four are cut off, generally four come 
back (Fig. 2, E)\ when five are cut off, four or five come back (Fig. 
2, F^ ; but if six or more are cut off, only four or five are regenerated 
(Fig. 2, G\ It is found in this case that a limit is soon reached beyond 
which fewer segments are produced than have been removed. The 
new segments form the anterior end or head that enlarges to the char- 
acteristic size; but the missing segments behind the new head are 
never regenerated, and the worm remains shortened throughout the 
rest of its life. If the reproductive region has been removed with 
the anterior part, new reproductive organs are never formed and 
the worm remains incapable of reproducing itself. 

This same relation between, the number of segments cut off 
from the anterior end and the number that is regenerated seems to hold 
good throughout the whole group of annelids, although the maximum 
number that comes back may be different in different species. Thus 
in lumbriculus six or seven or even eight new segments come back if 
more than that number have been removed. 

If we examine the method of regeneration from the posterior end 
of a piece of an earthworm, we find that when several or many 
posterior segments have been removed a new part comes back, com- 
posed at first of a very few segments. The terminal segment 
contains the new posterior opening of the digestive tract. New 
segments are now formed just in front of the terminal segment, the 
youngest being the one next to the end-segment The process con- 
tinues until the full complement of segments is made up (Fig. 3, 
Cy D, E). Comparing these results with those described above for 
the anterior end, we find, in both cases, that only a few segments 
are at first formed, but in the posterior regeneration new segments 
are intercalated near the posterior end. This process of interca- 
lation is the characteristic way in which many annelids add new seg- 
ments to the posterior end, as they grow larger and longer. 

Amongst the flatworms the fresh-water planarians show remark- 
able powers of regeneration. If the anterior end is cut off at any 
level, a new head is produced (Fig. 4, C). The new worm is at first 
too short, i.e. the new head is too near the pharynx, but changes 
take place in the region behind the new head that lead to the devel- 
opment of new material in this part. The new head is, in conse- 

1 These experiments on the earthworm are in the main taken from my own results ('95) 
C97) ('99). 



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10 



REGENERATION 



quence, carried farther and farther forward until the typical relations 
of the parts have been formed, when the growth in the region behind 
the head comes to an end (Fig. 4, O), Similar changes take place 
when the posterior end is cut off, as shown in Fig. 4, B, B^. The new 
part contains the new pharynx that is proportionately too near the 
head, but the pharynx is carried farther backwards by the formation 
of new material in front of it, until it has reached its typical distance 



.^^. 



1 1) 






'Fig, 4,^ A- E. Planar ia macvlata, A. Normal worm. B, B^. Regeneration of anterior half. 
C Ci. Regeneration of posterior half. D. Cross-piece of worm. Z?i, D^, D^, D*. Regenera- 
tion of same. E» Old head, /fi, £^, E^. Regeneration of same. E. P. lugubris. Old head 
cut off just behind eyes. F"^, Regeneration of new head on posterior end of same. 

from the head. In these planarians the results are somewhat com- 
plicated, owing to the old part changing its form, especially if the 
piece is not fed; but the main facts are given above, and a more 
complete account of the changes that occur will be given in another 
place. 

LATERAL REGENERATION 

Not only does regeneration take place in an antero-posterior direc- 
tion, but in many animals also at the side. The regeneration of the 
limb of the salamander is, of course, a case of lateral regeneration in 

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GENERAL INTRODUCTION II 

relation to the animal as a wh^ole, but in a longitudinal direction 
in regard to the limb itself. Lateral regeneration of the limb would 
take place if the limb was split lengthwise into two parts and one of 
the parts removed. If the entire salamander were cut in two length- 
wise, each half would most certainly die without regeneration, if for 
no other reason than that the integrity of the median organs is 
necessary for the life of the different parts. If, however, a planarian 
is cut lengthwise into a right and left half, each piece will complete 
itself laterally and make a new worm (Fig. 1 3^, A-D\ Even a narrow 
piece cut from the side will produce a new worm by regenerating 
laterally, as shown in Fig. 19, a, b, c. In hydra, also, a half-longi- 
tudinal piece produces a new animal, but in this case not by the 
addition of new material at the side, but by the cut-edges meeting 
to make a tube of smaller diameter. Subsequently the piece changes 
its form into that characteristic of hydra. 

REGENERATION OF TERMINAL PORTIONS OF THE BODY 

In njoait of the preceding examples the behavior of the larger piece 
of the two that result from the operation has been described ; but there 
are some important facts in connection with the regeneration of the 
smaller end-pieces. The leg, or the tail, that has been cut from the 
salamander soon dies without regenerating. The life of the leg can 
be maintained only when the part is supplied with certain substances 
from the body of the animal. It does not follow, of course, that, 
could the leg or the tail be kept alive, they would regenerate a 
salamander. In fact, there is evidence to show, in the tail at least, 
that, although it may regenerate a structure at its anterior end, the 
structure is not a salamander, but something else. This has been 
definitely shown in certain experiments with the tail of the tadpole. 
It is possible to graft the tail of one tadpole in a reversed position, 
i.e, with its anterior end free, on the tail of another tadpole (Fig. 54, 
A-D\ or even on other parts of the body. Regeneration takes place 
from the free end, i.e. from the proximal end of the grafted tail. 
The new structure resembles a tail, and not a tadpole. If it be 
objected that the experiment is not conclusive because of the presence 
of the old tail, or of the use of the newly developing part, the objec- 
tion can be met by another experiment. If, as shown in Fig. 56, A^ 
a triangular piece is cut out of the base of the tail of a young tadpole, 
the cut being made so deep that the nerve-cord and notochord are 
cut in two, there develops from the proximal end of the tail a new 
tail-like structure that is turned forward, or sometimes laterally. In 
this case the objections to the former experiment do not apply, and 
the same sort of a structure, namely, a tail, is produced. 

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12 



REGENERATION 



In the earthworm also we find some interesting facts connected 
with the regeneration of the terminal pieces. If one, two, three, 
four, or five segments are cut from the anterior end, they will die 
without regenerating. Pieces that contain more segments, six to 
ten, for example, may remain alive for a month or longer, but do not 
regenerate (Fig. 3, A, ^). That this lack of power to regenerate at the 
posterior end is not due to the smallness of the piece can be shown 
by removing from a piece of five segments one or two of its anterior 
segments. These will be promptly regenerated. Another experiment 



o o 





• 







0000 





YiG.$. — Hydra viridis, A. Normal hydra. Lines indicate where piece was cut out. B, 1-4. 
Changes in a piece of A, as seen from the side. C, 1-4. Same as seen from the end. A -£, 
F. Later stages of same piece, drawn to same scale. 

has shown, however, that if these small pieces can be kept alive for a 
long time, and also supplied with nourishment, regeneration will take 
place at the posterior end. If, for instance, a small piece of eight or 
ten segments has its anterior three or four segments cut off, ^nd is 
grafted by its anterior end to the anterior end of another worm, as 
shown in Fig. 3, F, the piece will begin, after several months, to re- 
generate at its exposed posterior end, but in the one instance in which 
this experiment has been successfully carried out, a new head, and 
not a tail, appeared on the exposed free end. The result is not due 
to the grafting, or to the anterior position of the posterior end, but to 

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GENERAL INTRODUCTION 



13 



some peculiarity in the piece itself. We find the converse of this 
result in an experiment with the tail region of the earthworm, where 
the outcome is more clearly seen to be connected with the nature of 
the piece itself. If a piece less than half the length of the worm is 
cut off from the posterior end, there is generally formed from its 
anterior cut-surface, not a head, but another tail (Fig. 2, /). The 
result is similar to that described by Bonnet for one of the fresh-water 
annelids. A parallel case to that of the head of the earthworm is 
found in one of the planarians. If the head of Planaria lugubris is 
cut off just behind the eyes (Fig. 4, F\ there is produced, at the pos- 
terior cut-edge of the head, a new head turned in the opposite direc- 
tion, as shown in Fig. 4, F^. 



r 



in 



REGENERATION BY TRANSFORMATION OF THE ENTIRE PIECE 

In the regeneration of some of the lower animals, the transforma- 
tion of a piece into a new animal of smaller size is brought about by a 
change in form of the piece itself, rather than through the production 
of new material at the cut-ends. If a ring is cut from the body of 
hydra, as shown in Fig. 5, A^ the open ends of the ring are soon 
closed by the contraction of the sides of the piece, and in the course 
of a few hours the ring has become a hollow sphere; or, if the 
piece is longer, a closed cylinder. After a day or two, the piece begins 
to elongate, and four tentacles appear near 
one end (Fig. 5, ^, C, D). The piece con- 
tinues to elongate until it forms a small 
polyp, having the typical proportions of 
length to breadth (Fig. 5, E, F). It has 
changed into a new cylinder that is longer 
than the piece cut off, but correspondingly 
narrower. In this case there cannot be said 
to be a replacement of the missing parts, 
but rather, through the transformation of 
the old piece, the formation of a new whole. 
In planarians also the formation of a new 
worm from a piece involves a change in the 
form of the old part, as well as the addition 
of new material at the cut-end. If a cross- 
piece is cut out, as shown in Fig. 4, A new 
material appears at the ends, but the old 
piece also becomes narrower and longer B 

(Fig. 4, D^-D' ). If the old head is cut off. >"«• ,t7„t ^'Zme "^^^^ 
it produces new material at its posterior end stnpe injured at two pomts 

._V -^ y^,. JIT. n (see circles m^). /?. Regen- 

(Fig. 4, E, E^\ and also becomes smaller eration of same^iece. j 

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14 



REGENERA TION 



as the new part grows larger (Fig. 4, £^ E^\ In a land planarian, 
Bipalium kewense, a piece is transformed into a new worm, as shown 
in Fig. 6, A, B. In this case the old pigment stripes of the piece are 
carried directly over into the new worm, the piece elongating during 
the transformation. 

A similar change takes place in pieces of unicellular animals, as 
best shown by cutting ofiF pieces of stentor. If Stentor cceruleus is 




Fig. 7. — Stentor caeruUus, A, Normal, fully expanded individual. A^, Same contracted. 
Line a-o indicates where it was cut in two. B, C, Pieces after division. B^, B^, B*. Re- 
generation of three distal pieces {B) containing old peristome. C^, 6'2. Regeneration of two 
proximal or foot pieces (C). 

cut in two pieces, as indicated ih Fig. 7, each piece makes a new 
individual of half size, but of proportionate form. The old peristome 
remains on the anterior piece, but becomes reduced in size as the piece 
changes its shape, and although it may be at first too large for the 
length of the new piece, it ultimately reaches a size about proportion- 
ate to the rest of the animal. The posterior pidce is at ftrst too long 

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GENERAL INTRODUCTION 



IS 



for the size of the new peristome that is formed, but the latter becomes 
larger, until the characteristic form has been reached. The change 
in form of the stentor may take place in a few hours, and the result 




I 





D 



Fig. 8. — After Gruber. Stentor coeruleus. A, Cut into three pieces. B. This row shows regen- 
eration of anterior piece. C. This row shows regeneration of middle piece. D. I'his row 
shows regeneration of posterior piece. 

is brought about, not by the development of new protoplasm over the 
cut-end, but by a change of the old protoplasm into the new form. A ^ 
similar experiment is shown in Fig. 8, in which a stentor was cut into 
three pieces, each piece containing a part of the old nucleus. 



REGENERATION IN PLANTS 

In the higher plants the production of a new plant from a piece 
takes place in a different way from that by which in animals a new 
individual is formed. The piece does not complete itself at the cut- 
ends, nor does it change its form into that of a new plant, but the 
leaf-buds that are present on the piece begin to develop, especially 
those near the distal end of the piece, as shown in Fig. 32, A, and 
roots appear near the basal end of the piece. The changes that take 
place in the piece are different from those taking place in animals, 
but as the principal difference is the development of the new part 
near the end, rather than over the end, and as in some cases the 

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i6 



REGENERATION 



new part may even appear in new tissue that covers the end, and, 
further, since the process seems to include many factors that appear 
also in animals, we are justified, I think, in including this process 
in plants under the general term regeneration. 




Fig. 9. — After VQchting. A, A^, A^. Pieces of thallus of Lunularia communis regenerating at 
the apical end. B. Piece of thallus cut in two in the middle line. B^. Same split at side of 
middle. C. An oblique piece extending to middle line. C^, C^. Oblique pieces not extend- 
ing to middle line. D. Fruiting stalk stuck into sand, producing new thallus above sand. 
D^, Same laid horizontally regenerating near base. E. Same with fruiting head cut off. 
Regenerating at base. E^. Twisted piece regenerating at two points. F. Piece of ray of 



head regenerating near base, 
at base. 



/'i. Same with distal end of ray cut off. Also regenerating 



In the lower plants, such as the mosses, the liverworts, the moulds, 
and the unicellular forms, regeneration also takes place. Vochting 
has shown that pieces from any part of the thallus of a liverwort ^ 
produce new plants. If a cross-piece is cut off, there appears a small 



1 Lunularia vulgaris. 



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GENERAL INTRODUCTION 



17 



outgrowth from the middle of the anterior cut-edge, as shown in 
Fig. 9, A, A^y that gradually enlarges to form a new thallus. It will 
be seen from the figures that the whole anterior edge does not grow 
forward, but a new thallus arises from a group of cells at, or near, 
the anterior edge. These cells are the least-differentiated cells in 
the piece, and have softer cell walls than have the other cells. 




Fig. la— After Pringsheira. A, A piece of seta of sporophore of Hyfnum cupressi forme, sending 
out protonema-threads. B. Longitudinal section of a piece of the seta of sporophore of 
Btyum ccsspitosum. C. Piece of same of Hypnum cupresslforme. Moss-plant arising from new 
protonema. D, Piece of same of Hypnum serpens with protonema and moss-plant arising 
irom it 

Pringsheim has shown that if a piece of the stalk of the sporan- 
gium of certain mosses is cut off, it produces at its ends thread-like 
outgrowths which are like the protonema-stage of the moss, and from 
this protonema new moss-plants may arise (Fig. lo^ Ay B, C^ D), 

Braefeld has obtained a somewhat similar result in one of the 
moulds, in which a piece of the sporangium stalk gives rise to a 
mycelium from which new sporangia may be produced. 

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i8 



REGENERATION 



REGENERATION IN EMBRYOS AND EGGS 

Regeneration takes place not only in adult organisms, but also in 
embryos, and larvae of many animals. It is often stated that the 
power of regeneration is more highly developed in embryos than in 
adults, but the facts that can be advanced in support of this view 
are not numerous. One of the few cases of this sort known to us 
is that of the leg of the frog, that does not regenerate, while the leg 
of the tadpole is capable of regenerating. 







®o®v 



OQOO V 



Fig. II. — A, Blastula of Sea-urchin. Dotted lines indicate where pieces of wall were cut off. To 
the right are shown stages in the development of these pieces. B. Two-cell stage of egg 
of sea-urchin. One blastomere isolated. Its development shown in figures to right of B, 
C Fertilized but unsegmented egg. Dotted line indicates where it was cut in two. Upper 
row of figures to right shows development of nucleated piece ; lower row shows the fertiliza- 
tion and development of non-nucleated piece. 

The early stages in the development of the sea-urchin, or of the star- 
fish, may be taken to illustrate the power of regeneration in embryos. 
If the hollow blastula of the sea-urchin is cut into pieces (Fig. ii. A), 
each piece, if not too small, may produce a new blastula. The 

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GENERAL INTRODUCTION 1 9 

edges of the piece come together, and fuse in the same way in which 
a piece of hydra closes. A new hollow sphere of small size is formed, 
which then passes through the later stages of development as does the 
whole normal blastula. 

Still earlier stages of the sea-urchin, or of the starfish, have the 
power of producing embryos if they are cut into pieces. If the seg- 
menting egg is separated into a few parts, each part will continue to 
develop. Even the first two blastomeres or cells will, if separated, 
produce each a whole embryo (Fig. ii, -ff). The power of develop- 
ment of a part does not even end here, for, if the undivided, fertilized 
egg is cut into pieces, the part that contains the nucleus will segment 
and produce a whole embryo (Fig. ii, C, upper row). If the Qg'g is 
cut in two or more pieces before fertilization, and then each part is 
fertilized, it has been found that not only the nucleated, but even the 
non-nucleated fragments (if they are entered by a single spermato- 
zoon) may produce embryos (Fig. ii, C, lower row). 

It may be questioned whether the development of parts of the 
embryo, or of the egg, into a whole organism can be included in the 
category of regenerative processes. There are, it is true, certain dif- 
ferences between these cases and those of adult forms, but as there 
are many similarities in the two cases, and as the same factors appear 
in both, we cannot refuse, I think, to consider all the results from a 
common point of view. 

PHYSIOLOGICAL REGENERATION 

Finally, there are certain normal changes that occur in animals 
and plants that are not the result of injury to the organism, and these 
have many points in common with the processes of regeneration. 
They are generally spoken of as processes of physiological regenera- 
tion. The annual moulting of the feathers of birds, the periodic loss 
and growth of the horns of stags, the breaking down of cells in dif- 
ferent parts of the body after they have been active for a time, and 
their replacement by new cells, the loss of the peristome in the proto- 
zoon, stentor, and its renewal by a new peristome, are examples of 
physiological regeneration. This group of phenomena must also be 
included under the term ** regeneration," since it is not sharply sepa- 
rated from that including those cases of regeneration after injury, or 
loss of a part, and both processes appear to involve the same factors. 

DEFINITION OF TERMS 

The older writers used such terms as " replacement of lost parts," 
"renewal of organs," and '* regeneration " to designate processes 
similar to those described in the preceding pages. The term regen- 

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20 REGENERA TION 

eration has been for a long time in general use to include all such phe- 
nomena as those referred to, but amongst recent writers there is some 
diversity of opinion as to how much is to be included in the term, and 
the question has arisen as to the advantage of applying new names 
to the different kinds of regeneration. There can be little doubt of 
the advantage, for the sake of greater clearness, of the use of different 
terms to designate different phenomena, but I think that there is at 
the same time the need of some general term to cover the whole field, 
and the word regeneration, that is already in general use, seems to 
fulfil this purpose better than any other. 

Roux^ points out that Trembley, and later Nussbaum, showed 
that a piece of hydra regenerates without the formation of new mate- 
rial. Roux adds that since during development the piece takes no 
nourishment, the regeneration must be brought about by the rearrange- 
ment of the cells present in the piece.^ The change may, or may 
not, involve an increase in the number of the cells through a process 
of division. In consequence of this mdthod of development a re-dif- 
ferentiation of the cells that have been already differentiated takes 
place. This process of regeneration, Roux points out, is very similar 
to the " post-generation " of the piece of the blastula of the sea-urchin 
embryo, and he concludes that "regeneration may be brought about 
entirely, or very largely, through the rearrangement and re-differen- 
tiation of cells without any, or with very little, proliferation taking 
place.'* In the adults of higher animals regeneration by prolifera- 
tion preponderates, but rearrangement and re-differentiation of cells 
occur in all processes of regeneration, even in higher vertebrates. 
The two kinds of regeneration that Roux distinguishes are, he says, 
essentially quantitative.^ 

1 Gesammelte Abhandlungen, No. 27, p. 836. 

3 The fact that the piece does, or does nc^t, take in food has no bearing on the question, 
since many animals that do not feed while the regeneration is going on produce new cells to 
form the new part. 

^ These two kinds of regeneration are post-generation and regeneration proper. The 
distinction that Roux attempts to make between these two processes is to a certain extent 
artificial and rests at present on a very unsafe basis, at least in so far as the post-generation 
of the frog's embryo is taken as a representative case of this process. Roux states that in 
the process of regeneration the injured tissues produce each their like in the new part, while 
in the process of post-generation of the frog's egg the new cell-material arises in part from 
the nuclei and yolk-material of the injured half and in part through the accidental posi- 
tion of the nuclear material of the uninjured half. In order more fully to understand this 
distinction the original description of the process of post-generation given by Roux in his 
account of the development of half embryos of the frog's egg must be referred to. In later 
papers Roux pointed out that the missing half of the frog eml)ryo, as well as of other forms, 
may be post-generated without any new material appearing at the open side of the embryo. 
It is unfortunate, 1 think, that the original term should have been extended to include these 
other processes that do not partake of the nature of post-generation as at Brst defined, but 
are more like the true process of regeneration as described by Roux. 

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GENERAL INTRODUCTION 21 

Barfurth^has defined regeneration as " the replacement of an organ- 
ized whole from a part of the same." If the part is given by nature, 
there is a process of physiological regeneration; if the part is the 
result of an artificial injury, the process is one of pathological re- 
generation. Barfurth includes in the latter category the production 
of a new, entire individual from a piece, as in hydra ; regeneration 
by proliferation, as in the earthworm; and also the development of 
pieces of an egg or of an embryo. 

Barf urth's definition of regeneration is unsatisfactory, since an egg 
is itself a portion of an organism that makes a new whole, and this 
sort of development is not, of course, as he himself points out, to be 
included in the term regeneration. Nor does the use of the word 
" replacement *' save the definition, since in many cases the kind of 
part that is lost is not replaced. The use of the word "pathological" 
to distinguish ordinary regeneration from physiological regeneration 
is, I think, also unfortunate, since it implies too much. There is noth- 
ing necessarily pathological in the process, especially in such cases as 
hydra, or as in the development of a piece of an egg where the piece 
is transformed directly into a new organism. Furthermore, in those 
cases in which (as in some annelids and planarians) a new head is 
formed after or during the process of natural division, there is little 
that suggests a pathological process ; and in this instance the regen- 
eration takes place in the same way as after artificial section. 

Driesch, in his Analytische Theorie, states that Fraisse and Bar- 
furth have established that during regeneration each organ produces 
only its like. Driesch defines regeneration, therefore, as the re-awak- 
ening of those factors that once more bring into play, by means of 
division and growth, the elementary processes that had ceased to act 
when the embryonic development was finished. This is regeneration 
in the restricted sense, but Driesch also points out that this definition 
must be enlarged, since, when a triton, for example, regenerates its 
leg, not only does each tissue produce its like, but later a reconstruc- 
tion and differentiation takes place, so that a leg and foot are formed, 
and not simply a stump containing all of the typical tissues. Driesch 
holds that regeneration should include only those cases in which a 
proliferation of new tissue precedes the development of the new part, 
and suggests that other terms be used for such cases as those of pieces 
of hydra, pieces of the ^^g, etc., in which the change takes place in 
the old part without proliferation of new tissue. It seems to me 
unwise to narrow the scope of the word regeneration as Driesch pro- 
poses, for it has neither historical usage in its favor, nor can we make 
any fundamental distinction between cases in which proliferation 
takes place and those in which it does not. As will be shown later, 

^ Ergebnisse der Anatomie und Entwickelungsgeschichte. 1891-1900. 

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22 REGENERATION 

the factors that are present in the two cases appear to be in large part 
the same, and while it may be convenient to put into one class those 
cases in which proliferation precedes the formation of the new organs, 
and into another class those cases in which the change takes place 
without proliferation, yet, since the distinction is one of subordinate 
value, it is necessary to have one word to include both groups of 
cases ; and no better word than regeneration has, I think, been as yet 
suggested. 

Driesch has made use of two other descriptive terms. The word 
" reparation " is used to describe the development of the Ji^dranth of 
tubularia. The new hydranth is formed in this case out of the old 
tissue at the end of the piece (Fig. 20, A), The change appears to be 
the same as that which takes place in a piece of hydra, etc. The word 
" reparation " does not seem to me to express very satisfactorily this 
sort of change, or sharply separate it from those cases in which the 
animal is repaired by adding what has been taken away ; but in this 
latter sense Driesch does not use the term. I have not made use of 
the word, in general, except as applied to Driesch*s work. 

Another term, "regulation," used by Roux,^and also by Driesch and 
others, is used in a sort of physiological sense to express the readjust- 
ments that take place, by means of which the typical form is 
realized or maintained. By inference we may extend the use of the 
word to include the changes that take place in the new material, that 
is proliferated in forms that regenerate by this method. Driesch 
uses this term, regulation, to include a much more general class of 
phenomena than those included in the term regeneration, as for in- 
stance, the regulation of metabolism and of adaptation, etc. One of 
the subdivisions of the term regulation is called "restitution." This 
word also is used where I should prefer to use the word regeneration as 
a general term, and the word reorganization when reference is made 
to the internal changes that lead to the production of a typical 
form. 

Both Roux and Driesch also speak of " self-regulation," by which is 
meant, I suppose, that the changes taking place are due to readjust- 
ments in the part itself, and are not induced by outside factors. The 
expression " self-regulation " is not, I think, a very happy one, since 
all change is ultimately dependent upon a relation between inside and 
outside conditions. 

Hertwig^ defines regeneration as the power of replacement of a 
part of the organism. He states that in all cases the beginning of 
the process is the same, viz. the appearance of a small protuberance 
composed of cells, that is the rudiment of the new part. It is evident 

^ As used in connection with other terms, see his Ges. Abhandl., Vol. II, page 41. 
* Die Zellc und die Gewebe. 



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GENERAL INTRODUCTION 23 

that Hertwig has taken into account only one side of the process. 
Those cases in which a rearrangement or reorganization takes place 
in the old part are not even considered.^ Goebel^ points out that in 
plants the fully formed cells are, as a rule, incapable of further growth 
after they have once served as a basis of an organ of the body, but 
often some of the cells may remain in a latent condition, and grow 
again, when the intercellular interactions are disturbed. This is the 
case, he thinks, in regeneration. Goebel speaks of regeneration by 
means of adventitious buds in those cases in which the buds had not 
previously existed before the removal of the part. In those cases in 
which the buds are in existence before the piece is removed, as in 
the leaves of Asplenium, Begonia, etc., the development is not the 
result of regeneration, Goebel thinks, but the buds represent a stage 
in the development of the species. It may be pointed out, however, 
that it is certainly a remarkable fact that often the conditions that 
lead to the unfolding of an existing bud are the same as those that 
lead to the development of a new bud. 

The preceding account will suffice to illustrate some of the princi- 
pal ideas that are held in regard to the process of regeneration. 
Since many new facts have come to light in the last few years, it may 
not be amiss to point out what terms will be used in the following 
pages to include each kind of process. 

The word " regeneration " has come to mean, in general usage, not 
only the replacement of a lost part, but also the development of a 
new, whole organism, or even a part of an organism, from a piece of 
an adult, or of an embryo, or of an egg. We must include also those 
cases in which the part replaced is less than the part removed, or even 
different in kind. 

At present there are known two general ways in which regenera- 
tion may take place, although the two processes are not sharply 
separated, and may even appear combined in the same form. In^ 
order to distinguish broadly these two modes I propose to call those 
cases of regeneration in which a proliferation of material precedes the 
development of the new part, "epimorphosis." The other mode, in 
which a part is transformed directly into a new organism, or part 
of an organism without proliferation at the cut-surfaces, " morphal- 
laxis." 

In regard to the form of the new part, certain terms may be used 
that will enable us to characterize briefly different classes. When the\ 
new part is like that removed, or like a part of that removed, as when / 
a leg or a tail is regenerated in a newt, the process is one of "homo-j 

1 Hertwig's description of the method by which a piece of Jiydra makes a new one shows 
that he did not understand the kind of change that takes place in this animal. 

«OrganographiederPflanzen.-98. Digitized by GoOglC 



24 



REGENERATION 



morphosis." ^ Under this heading we may distinguish two cases, in one 
of which the entire lost part is at once, or later, replaced — holomorph o- 
^is^ in the other the new part is less than the part removed — niero- 
morphosis» When the new part is different from the part removed the 
process hasbeen called by Loeb " h gteromorphosis ," but there are at least 
two different kinds of processes that are covered by this definition. 
In one case the new part is not only different from the part removed, 
but is also an organ that belongs to a different part of the body (or it 




Fig. 12. — After Herbst. Diagram showing brain, eye, and " heteromorphic " antenna (in place 
of eye of one side) of palaemon. The animal had lived in a dark aquarium for five months. 

may be unlike any organ of the body). This we may call "jieomor- 
pJiesis.*' As an illustration of this process may be cited the develop- 
ment of an antenna, when the eye of a crab or of a prawn is cut off 
near the base (Fig. 12); and as an example of an organ different in 
kind from any organ of the same animal, may be cited the case of 
Atyoida potimimm, in which the new leg is unlike any other leg on 
the body. The name " heteromorphosis " can be retained for those 
cases in which the new part is the mirror figure of the part from 
which it arises, or more generally stated, where the new part has 

1 This term is used by Driesch in his Analytische Theories 



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GENERAL INTRODUCTION 2$ 

its axes reversed as compared with the old part. As an example of 
this may be cited the development of an aboral head on the pos- 
terior end of a piece of the stem of Tubularia (Fig. 15, B\ or the 
development of a tail at the anterior end of a posterior piece of an 
earthworm (Fig. 2). 

The term ** physiological regeneration " I shall use in the ordinary 
sense to include such changes as the moulting and replacement of 
the feathers of birds, the replacement of teeth, etc., — changes that 
are a part of the life-cycle of the individual. In some cases it can 
be shown that these processes are closely related to ordinary re- 
generation, as when a feather pulled out is formed anew without 
waiting for the next moulting period, and formed presumably out of 
the same rudiment that would have made the new feather in the 
ordinary moulting process. 

It is sometimes convenient to contrast the process of physiological 
regeneration with all other kinds. The use of the term ** pathological 
regeneration " for the latter seems to me, as has been said, unsatisfac- 
tory. The two terms proposed by Delage,^ viz. ** regular regeneration " 
and "accidental regeneration," have certain advantages, although 
there is nothing accidental, or at least occasional, in regard to the pro- 
cess itself, as it is entirely regular, although it may only occur after 
an accident to the animal. The term " regular regeneration " is, I 
think, more satisfactory than ** physiological regeneration," but the 
latter has the advantage that it has come into current use. For what 
is known as pathological or accidental regeneration, I propose the 
term " restorative regeneration," and I shall continue to use the 
term "physiological regeneration" as generally understood. 

1 Delage, Y, La Structure du Protoptasmoy etc., '95. 



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CHAPTER II 

THE EXTERNAL FACTORS OF REGENERATION IN ANIMALS 

There is a constant interchange of material and of energy that 
takes place between a plant or an animal and its surroundings, and 
this interchange may be influenced by such physical conditions as 
temperature, light, gravity, etc., or by such chemical conditions as 
the composition of the atmosphere or of the water surrounding the 
organism. We can study the process of regeneration either by keeping 
the regenerating organism under the same conditions that it is subject 
to in its natural environment, or else we can change the surrounding 
physical or chemical conditions. In this way we can determine how 
far the regeneration is affected by external changes, and how far it is 
independent of them. If a change in the external conditions pro- 
duces a definite change in the regeneration, then the new condition is 
called an external factor of regeneration. 

TEMPERATURE 

That the rate at which regeneration takes place can be influenced 
by temperature has been shown by Trembley, Spallanzani, Bonnet, 
and by many more recent writers. In fact, so familiar is the process 
to every one who has studied regeneration, that it is usually taken for 
granted that such is the case. 

In general it may be stated that the limits of temperature under 
which normal growth may take place represent also the limits of 
temperature for regeneration. Lillie and Knowlton ('97) have deter- 
mined the limits of temperature within which regeneration takes 
place in Planaria toma. The worm was cut in two transversely 
through the pharynx, and the time required at different temperatures 
to produce a new head on the posterior piece was recorded. The 
lowest temperature at which regeneration was found to take place 
was 3°C. Of six individuals kept at this temperature only one regen- 
erated at all, and in this one the eyes and brain were still incomplete 
after six months. The optimum temperature, or at least that at 
which regeneration takes place most rapidly, was found to be 29. 7° C; 
a new head developed in 4.6 days at this temperature. At 31.5*^0. 

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EXTERNAL FACTORS OF REGENERATION IN ANIMALS 



27 



regeneration was slower, requiring 8.5 days to make a new head. At 
32° C. incomplete regeneration sometimes , took place, but death 
occurred in about six days. At 33° C. regeneration was very slight, 
and the animals died within three days. At 34° C, and above this 
point, no regeneration took place, and death soon occurred. 

In Hydra viridisy Peebles ('98) has found that regeneration is 
quicker at 26*^-27° C. than at 28°-30° C. At the former temperature 
regeneration takes place in 48 hours. If kept at I2°C. pieces may 
regenerate in 96 hours, but not all the pieces had regenerated in this 
case until 168 hours. 




INFLUENCE OF FOOD ON REGENERATION 

While the growth of an animal or of a plant is, in most cases, and, 
of course, within certain limits, directly connected with the amount 
of food that is obtainable, nevertheless extensive regeneration may take 
place in an animal, or part of an animal, entirely deprived of food. In 
this case the material for the new part is derived from the excess of 
material in the old part, and not only surplus 
food material, but even the protoplasm itself 
appears to be drawn upon to furnish material 
to the new part. The relation between regen- 
eration and the amount of food present in the 
old part is well shown by experiments with 
planarians. If a planarian is kept for several 
months without food, it will decrease very 
much in size. In fact, the volume of a 
starved worm of Planaria btgubris compared 
with that of a fully fed individual may be only 
one-thirteenth of the latter (Fig. 13, A, B), 
If a starved worm is cut in two pieces, 
each piece will regenerate, although less 
quickly than in a well-fed worm. The new 
part will continue to increase in size at the 
expense of the old piece that is already in a 
starved condition. On the other hand, an 
excess of food does not necessarily produce a 
hastening of the regeneration, for, as Bardeen 
('01) has shown, worms that have been for several days without food 
may regenerate more quickly than worms that have been fed just 
before they were cut into pieces. 

The growth of the new part at the expense of the old tissues is a 
phenomenon of the greatest importance, an explanation of which 
will involve, I think, the most fundamental questions pertaining to 

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Fig. 13.— Drawn by N. M. 
Stevens. A. Large well- 
fed individual of Planaria 
lugubrii. B. Same after 
being kept without food 
for 4 mos. 13 days. Both 
drawn to same scale. 



28 



REGENERATION 



growth. The results show that growth is connected with a structural 
factor, and is not simply a physiological phenomenon, although no 
doubt physiological factors are involved. But the physiological factors 
that are here at work seem to be different from what is ordinarily 
understood ; for the fact that a tissue that is slowly starving to death 
should be reduced still further, and at a more rapid rate, in order to 
supply material to a new part, is certainly a remarkable phenomenon. 





vl 



xix 



W 






Fig. \\\. ^ Planaria luguhris. Dotted line indicates where the worm was cut in two lengthwise. 
Upper three figures show how a half, that is being fed, regenerates. Lower three figures show 
other half kept without food. 

At present we are not in a position to offer any explanation that rests 
on observation, or experiment, as to how the transfer of material takes 
place, or as to how the new tissue manages to get hold of the mate- 
rial from other parts. It is possible to protect the old part to a large 
extent by keeping the regenerating piece well supplied with food. If 
a well-fed planarian is cut in two along the middle line of the body 
as indicated in Fig. 13 J, A, there develops, in the course of five or six 
days after the operation, new material along the cut-s|de of each 

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EXTERNAL FACTORS OF REGENERATION IN ANIMALS 29 

piece, and a new pharynx appears at the border between the old and 
the new parts. If one of the pieces is fed at intervals, it is found 
that the new part grows more rapidly than does the new part in the 
piece without food. The old tissue in both pieces has shortened 
somewhat after the operation, and has also decreased somewhat in size 
as the first new material developed along the cut-side, but in the 
piece that is fed the old half begins to increase again until it reaches 
its former size, and may even surpass the latter. A large full-sized 
worm is produced from this piece, as shown in Fig. 13 J, B^ C, D, In 
the starved piece the old part continues to grow small, due to the lack 
of food and also to the increase in the new side. This increase takes 
place very slowly, but ultimately a small symmetrical worm may be 
produced, as shown in Fig. 13^,^, Fy G. It will be seen that the 
starved piece needs to produce relatively less and less new material 
in order to become symmetrical, because as the old material diminishes, 
the pharynx comes to lie nearer to the middle line. 

EFFECT OF LIGHT ON REGENERATION 

Although few experiments have been made to test the effect of 
light on regeneration, it is certain that in many cases light has no 
effect on the process, neither as to the quality nor the quantity of the 
result In one form, a tubularian hydroid, Eudendrium racemosum^ 
it has been shown by Loeb that the regeneration of the hydranth- 
takes place only when the animal is exposed to light. When a 
colony of eudendrium is brought into the laboratory and placed in an 
aquarium, the hydranths soon die ; but if the colony is kept in a lighted 
aquarium, new hydranths are regenerated in a few days. If, on the 
other hand, the colony is kept in the dark, new hydranths do not 
appear ; but if it is brought back again into the light the hydranths 
appear. In one experiment one lot of pieces was kept in diffuse day- 
light, and another lot in the dark. The former produced fifty new 
hydranths in a few days; those in the dark had not made any 
hydranths after seventeen days. They were then brought into the 
light, and in a few days several hydranths had developed on each 
piece. 

Loeb also tried the effect of different colored light on the regen- 
eration of eudendrium. Dishes containing pieces of the hydroid were 
put into a box that was covered by colored glass plates. Pieces sub- 
jected to dark red and to dark blue light gave the following results. 
The old hydranths, as is generally the case, were absorbed in the 
course x)f three days. The first new hydranths appeared in the blue 
light on the fourth day, and during the following days the hydranths 
in this lot steadily increased. Eight days after the beginning of jthe 

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30 REGENERATION 

experiment there were eighty hydranths under the blue glass, but not 
one had developed in the red light. On the ninth day the red glass 
was replaced by a dark blue one. Two days later hydranths began to 
appear, and on the following day thirty-two hydranths had appeared, 
and in a few days more as many as sixty had developed.^ Loeb con- 
cluded that only in the more refrangible (blue) rays does the regen- 
eration of the hydranth take place, while the less refrangible (red) 
rays act as darkness does.^ This hydroid is the only animal yet 
found that shows the effect of light on regeneration, and it is inter- 
esting to find that it is one of the few animals known in which light 
has an influence on the growth, if the heliotropism, or turning towards 
the light, of the hydranth is looked upon as a phenomenon of growth. 
There is another series of experiments made to test the effect of 
light on regeneration, which gave, however, negative results. Herbst 
observed that when the eye of certain Crustacea^ is cut off, some- 
times an eye and sometimes an antenna is regenerated. A number 
of individuals from which the eyes had been removed were kept in 
the light, and others in the dark, in order to see if the presence or 
absence of light is a factor in determining the Tcind of regeneration 
that takes place. It was found that as many individuals regenerated 
eyes in the dark as in the light. It was discovered later by Herbst 
and myself, independently, that, when the end only of the eye-stalk is 
cut off, an eye regenerates, but when the eye-stalk is cut off at the 
base, an antenna regenerates. The difference in the result has there- 
fore no connection with the presence or absence of light. 

GRAVITY 

The only case known amongst animals, in which regeneration is 
influenced by the action of gravity,* is that of the hydroid Antennu- 
laria antennina. This hydroid lives attached to the bottom of the 
sea several metres below the surface. The hydroid consists of a 
single, vertical, central stem, or axis, with two or four series of lateral 
branches along which the hydranths arise (Fig. 14, A\ The stem is 
attached by so-called stolons, or roots. In its normal growth at the 
free end the hydroid has been shown by Loeb to exhibit marked 
geotropic changes. If, for instance, the stem is bent over to one side 
the new growth that takes place at the apex of the stem directs the 
new part upwards in a vertical direction. 

If pieces are cut from the stem of antennularia and suspended in 

^ The dark red glass was fairly monochromatic; the dark blue let a trace of red light 
through. 

^ The same difference was found in this form in regard to heliotropism. 

' Palaemon and Sicyonia. 

* The regeneration of the lens of triton may also be affected by gravity. ^-^ , 

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EXTERNAL FACTORS OF REGENERATION IN ANIMALS 



31 



the water, regeneration takes place at the cut-ends. If a piece is 
suspended with its apical end upwards (Fig. 14, B\ a new stem devel- 
ops at the upper cut-end, and new roots from the lower cut-end. 
If a piece is suspended with its basal end upwards (Fig. 14, C), there 
is formed at its upper (basal) end a new stem with its branches also 
slanting upwards as shown in the figure. Roots appear at the 





Fig. 14. — After Loeb. Noiroal stalk of Aniennularia antennina. B, Piece regenerating in vertical, 
normal position. C. Piece regenerating in inverted position. D. Piece regenerating in in- 
clined, vertical position. E. Piece regenerating in inclined, inverted position. F, Piece 
regenerating in horizontal position. 

lower (apical) end. Since gravity is the only force that acts in a 
vertical direction under the conditions of the experiment, Loeb con- 
cluded that it plays an important r61e in determining the kind of 
regeneration that takes place. Its action is of such a nature that a 
new stem develops from the upper cut-end, and roots from the lower 
end, regardless of whether the upper end is the basal or the apical 
end of the piece. Similar results are also obtained, according to 

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3 2 HE GENERA TION 

Loeb, if the pieces are suspended obliquely. In a piece of this sort, 
it is found that new stems arise along the upper surface of the old 
stem, and roots from the lower surface as well as from the lower 
cut-end (Fig. 14, D^ E). If a piece of the stem is placed horizontally 
on the bottom of an aquarium, the branches that come off from the 
under surface of the stem begin to grow downwards at their ends, 
and where they come in contact with a solid body they fasten them- 
selves to it, thus showing that they are true roots (Fig. 14, F), One 
or more stems may arise from the upper side of the main stem. 
These stems' grow vertically upwards, and produce lateral branches. 
Only in one case did a new stem, or stem-like structure, arise from 
one of the vertical branches, as shown to the left in Fig. 14, F. 

Loeb found it also possible to change the character of the growth 
of the apex of the normal stem and to transform it into a root. A long 
piece of the hydroid was cut off and suspended vertically with the 
basal end upwards. From the upper end a new stem began to grow, 
and then the entire piece was reversed, so that the new stem pointed 
downwards. Under these circumstances the young stem did not 
bend around and begin to grow upwards, as a young plant might 
have done, but it ceased to grow as a stem, and at its apex one or 
more roots developed. Loeb concludes: "I cannot imagine by 
what means the place of the formation of organs in antennularia 
is determined in connection with the orientation of the animal except 
by means of gravity.*' 

The response of antennularia to the action of gravity is, I think, 
conclusively demonstrated by Loeb's results, but that the phenomenon 
may be complicated by other factors is shown, I think, by the follow- 
ing experiments. Driesch found that if pieces of antennularia are 
cut off and placed between horizontal plates, so that both ends are 
free, roots are produced by the basal end.^ If the basal end with its 
new roots is cut off, new roots may appear, but sometimes a thin 
stem also. If the end is again cut off, a larger stem, and also one or 
two roots, may appear, and if the operation is repeated again only 
a stem is formed. The factor that brings about this change is not 
shown by the experiment. The piece had been kept in a horizontal 
position throughout the whole time. The apical end died in most 
cases without producing roots, but it is not stated whether or not 
roots appear on the stem between the plates of glass. If they 
develop they may affect the result, as certain experiments that I have 
made seem to show. 

In my experiments, made at a different time of year from that at 

1 Driesch does not give in his paper (*99) the position of the hydroids, or the method of 
the experiment, but I can supply the details given above from a personal communication 
from Driesch. 



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EXTERNAL FACTORS OF REGENERATION IN ANIMALS 33 

which Loeb's experiments were made, pieces of the stem were sus- 
pended vertically, — some with the apical end upwards, others with the 
basal end upwards. In nearly all cases roots were formed by both 
the upper and lower ends. In a few cases, in which the apical end 
was upwards, a new stem developed at that end. Pieces suspended 
in a horizontal position also produced roots at both ends. After 
removing the ends with their new roots from the pieces suspended 
vertically, I found that roots again appeared at both ends in nearly 
every case. The difference between these results and those of Loeb 
may be due to the time of the year at which the experiments were 
made, or possibly to some other difference, but the results show that 
the response to gravity is not always so constant as Loeb*s results 
indicate. 

In a few cases in my experiments the basal end of the hydroid was 
left attached to the stem on which it had grown, and the piece was 
put into the same aquarium used for the preceding experiments. In 
those pieces that lay on the bottom of the aquarium, with the stem 
standing vertically, a new shoot, and not new roots, appeared on the 
upper end. Other pieces were hung at the top of the water of the 
aquarium with the stem turned downwards, and the basal, attached 
end of the piece upwards. These pieces produced neither a stem nor 
roots from the apical end. The results show that the presence of 
roots at one end has an influence on the regeneration at the other 
end. The same thing was shown in one case in which a short piece 
sank to the bottom of the dish and, developing roots at its basal end, 
became fixed : a stem grew out of the apical end. 

A number of other experiments that I made, in which pieces of 
antennularia were fixed to a rotating wheel, gave negative results, 
since neither roots nor stems appeared on the pieces. The rubbing 
of the ends of the piece against the water as the wheel turned round, 
or else the agitation of the water, prevented, most probably, the 
regeneration from taking place. 

How gravity acts on antennularia has not as yet been determined. 
The only suggestion that we can offer at present is that it brings 
about a rearrangement of the lighter and heavier parts of the tissues. 
A rearrangement of this sort has been demonstrated when the egg of 
the frog is inverted, and in consequence certain changes are brought 
about in the development that will be described in another chapter. 

EFFECT OF CONTACT 

The contact of a newly forming part with a solid body has been 
shown by Loeb in a few cases, at least, to be a factor in regeneration. 
If a piece is cut from the stem of the tubularian hydroid Tubularia 

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34 



REGENERATION 



mesembryanthemum, and the piece held so that its basal end comes in 
contact with a solid body, a root develops at that end. If a piece is 
held in a similar position, but with its apical end in contact with 
a solid body, a root does not develop from this end. Evidently the 
development of a root in this form is also connected with an internal 
factor ; but that there is in reality a reaction in this case, and not sim- 
ply the development of a root at the basal end, is shown by the f ollow- 




FiG. 15. — After Loeb. A. A piece of the stem of margelis placed in a dish. Roots come off 
where stem touches dish, and polyps at other points. B. Piece of the stem of tubularia pro- 
ducinj; a hydranth at eacli end. C. Cerianthus membranaceus. Piece cut from side produc- 
ing tentacles only on oral side of cut. 

ing experiment : If a piece is cut from the stem and suspended so that 
both ends are surrounded by water — it makes no difference whether 
the piece is vertical or horizontal — a hydranth develops first on the 
apical end, and then another on the basal end (Fig. 15, B\ When 
the apical end of a piece is stuck in the sand, leaving the basal end 
free, a hydranth develops on the latter, but not on the end in the sand. 
In another hydroid, Margelis carolifiensis, studied by Loeb, the 
effect of contact is more easily demonstrated. If a branch of margelis 



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EXTERNAL FACTORS OF REGENERATION IN ANIMALS 35 

is put into a dish of water and is kept from all motion, the parts that 
come in contact with the dish produce roots that attach themselves. 
Even the apical end of the stem may grow out as a root, as shown in 
Fig. 15, -^. Those parts of the branch that are not in contact with 
any solid object give rise to new hydranths. Another hydroid, Pen- 
naria tiarellUy also shows, according to Loeb, the same response to 
contact. In this connection it is interesting to find that a growing 
hydranth of pennaria, if brought in contact with a solid body, turns 
away from the region of contact and bends at right angles to the body 
which it touches. We find, once more, that a factor having an influ- 
ence on the growth of the animal has also a similar influence on the 
regeneration. 

Loeb has found that if pieces of the hydroid Campanularia are cut 
ofif and placed in a dish filled with sea water, all the hydranths that 
touch the bottom of the dish are absorbed and transformed into the 
substance of the stem. The ccenosarc may creep out of the stem 
wherever it comes in contact with the glass, and produce stolons that 
give rise to new polyps on their upper surfaces. Loeb shows that 
growth takes place at the end of the stolon that pushes out of the 
perisarc, and this growing region draws the rest of the ccenosarc after 
it. If a new hydranth appears along the old piece, the ccenosarc is 
drawn towards the hydranth. 

EFFECT OF CHEMICAL CHANGES IN THE ENVIRONMENT 

Temperature, light, gravity, and contact are the most familiar kinds 
of external physical agencies that have a direct influence upon the 
growth of organisms. Food, though coming from the outside, yet acts 
only after it has entered the body. Organisms that live in water may 
be affected by the quantity and the kinds of the salts contained in the 
water, and also by the dissolved gases. The only experiments that 
have been made to show the influence of this last class of agents on 
animals are those made by Loeb. He placed pieces of the stem of 
tubularia in sea water of different degrees of concentration. After 
eight days the pieces, that had meanwhile produced hydranths, were 
measured. It was found that the maximum growth in length takes 
place, not in normal sea water, but in a much diluted solution. Loeb 
interprets this result to mean that the cells of tubularia must have a 
certain amount of turgidity in order to grow, and this is possible so 
long as the concentration does not pass a certain limit. This limit is 
reached by the addition gf 1.6 grams of sodium chloride to each 100 
CO. of sea water. With a decrease in the concentration, the cells 
become more turgid, the maximum point corresponding to the 
maximum amount of growth. Below this point the solution is sup- 

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36 REGENERATION 

posed to act as a poison. The most important result of this experi- 
ment is to show that the maximum growth does not take place in sea 
water in which the animal is accustomed to live, but in a much more 
dilute solution. Normal sea water contains about 3.8 per cent of 
salts ; the maximum growth takes place in a solution containing only 
2.2 per cent. Not only is the length of the stem greater in the latter 
solution, but the thickness of the stem is also greater. The stem 
is smaller in a solution containing more salt than that contained in 
ordinary sea water. 

There is another variant in these solutions which Loeb takes into 
account. With the increase in concentration of the solution its power 
of absorbing oxygen decreases, but the difference is too slight to 
affect the main result. 

Not only does the amount of salts in solution affect the osmotic 
condition of the cells, but the salts also play a part in the metabolism 
of the animal. As the result of a series of experiments, the details of 
which may be here omitted, Loeb has shown that the regeneration of 
tubularia takes place only when the salts of potassium and of magne- 
sium are present. A very little of the potassium salt is necessary, 
too much retards, and still more prevents regeneration. 

There must be also a certain amount of oxygen dissolved in sea 
water in order that regeneration may take place. If a piece of the 
stem of tubularia is cut off and one end pushed into a small tube 
that fits the stem closely, and if the tube is then stuck into the sand 
at the bottom of an aquarium, a hydranth develops only at the free 
end of the piece, and none at the end in the tube. The result 
appears to be due to the lack of oxygen. If the piece is then taken 
from the tube, a hydranth may appear at the end that has been in 
the tube. 

Another experiment shows the same result even more clearly. If 
a piece of the stem is suspended freely in the water, so that its lower 
end is almost in contact with the surface of the sand, but does not 
quite touch it, no regeneration takes place at the lower end. This 
result is interpreted by Loeb as due to the lack of oxygen in the 
water near the surface of the sand.^ 

GENERAL CONSIDERATIONS 

In connection with the action of external factors on regeneration it 
is evident that in some cases they may not be in themselves necessary 
for the growth of a new part, yet when growth takes place they may 
determine what sort of a part is produced. For instance, if gravity 

1 Jacobson has shown that the layer of water just above the sedimentary layer at the 
bottom is poor in oxygen. 

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EXTERNAL FACTORS OF REGENERATION IN ANIMALS 37 

determines the kind of regeneration in antennularia, it is possible that 
if the regenerating piece were placed on a rotating wheel, the piece 
might still produce a new stem at the apical end, and roots at the 
lower end. In an experiment of this sort that I made, the pieces did 
not, it is true, regenerate at all, but this was probably due not to the 
change of position in regard to gravity, but to agitation of the water, 
or to the rubbing of the cut-end against the water. It is also possible 
that in this form the attachment of the piece at one end may be a 
factor that may counterbalance the action of gravity. Other factors, 
such as food, or temperature, or oxygen, appear not to determine the 
kind of product that results, but only the rapidity with which the 
change takes place. The salts in solution seem also to act on 
the rate and extent of the new growth, but possibly other cases may 
be found in which the kind of regeneration may also be affected by 
the salts. 

It is important to find that those animals whose growth and regen- 
eration are influenced by such external factors as light, gravity, and 
contact are attached animals that stand in a constant relation to these 
physical agents. They form only a very small part of the entire 
number of animals in which regeneration takes place. Animals 
that constantly move about are not, as a rule, influenced during 
their growth and regeneration by gravity and contact, and under 
natural circumstances they are always changing their position in 
regard to these agents. Temperature, and food, and substances in 
solution act alike on fixed and free forms, and they are, it appears, 
both influenced in the same way by these agents. The most signifi- 
cant fact that has been discovered in connection with the influence of 
external factors on regeneration is that the same factors that influ- 
ence the normal growth of the organism also affect in the same way 
the regeneration. 

As yet an analysis of the external factors that influence growth has 
not been made out as completely for animals as for plants, especially 
in those cases in which the result is determined by several factors 
at the same time. An examination of the factors that influence 
regeneration in plants will be made in a later chapter. First, how- 
ever, the internal factors of regeneration in animals will be consid- 
ered. 



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CHAPTER III 

THE INTERNAL FACTORS OF REGENERATION IN ANIMALS 

The comparatively few cases in animals in which regeneration has 
been shown to be influenced by external factors have been given in 
the preceding chapter. In all other cases that are known the factors 
are internal. By this is meant that we cannot trace any direct 
connection between the result and any of the known external agents 
that have been shown in other cases to have an influence on regener- 
ation. Certain external conditions must, of course, be present, such 
as a supply of oxygen, a certain temperature, moisture in some cases, 
etc., in order that the process may go on, but they are without 
influence on the kind of regeneration, and are necessary for all parts 
alike. 

POLARITY AND HETEROMORPHOSIS 

Trembley, Spallanzani, and Bonnet knew that, in general, at the 
end of a piece of an animal from which a head has been cut off a 
new head develops, and from the posterior cut-surface of a piece a 
new posterior part is regenerated. AUman was the first to give the 
name " polarity " to this phenomenon.^ 

In several animals regeneration takes place more readily from one 
, end than from the other of the same cut, and this difference seems 
to be connected with the kind of new part that is to be regenerated, 
and not with the actual power of regeneration of the region itself. 
For instance, if a short piece is cut from the anterior end of an earth- 
worm, a new anterior end is quickly regenerated from the anterior 
cut-surface of the posterior piece, but no regeneration takes place, or 
only after a long time, from the posterior cut-surface of the anterior 
piece. These relations are reversed if the posterior end of a worm 
is cut off. There regenerates very quickly a new posterior end from 
the posterior cut-surface of the anterior piece, but no regeneration 
takes place, or only after a long time, from the anterior cut-surface of 
the posterior piece. The new structures that develop after a long 
time from the posterior surface of a short anterior piece, and from 

^ "There is thus manifested in the formative force of the tubularia-stem a well-marked 
polarity^ which is rendered very apparent if a segment be cut out from the centre of the 
stem." AUman ('64). 

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INTERNAL FACTORS OF REGENERATION IN ANIMALS 



39 



the anterior surface of a short posterior piece, correspond to a differ- 
ent part of the worm from that which would be expected to develop, 
if the polarity of the piece is taken into account. Another reversed 
head develops on the posterior cut-surface of the anterior piece, and 




Fig. i6. — A, Head of Planar ia lugubris with line indicating level at which A^ was cut off. 
A^. Head of last regenerating a new head at its posterior end. B. Piece of P, maculata re- 
generating head at each end. C. Posterior end of Allolobophora foeiida regenerating a new 
tail at its anterior end. C^. Enlarged anterior end of last with new tail. c\ Tip of new tail. 
D, Anterior end of one individual of A. fxtida, grafted to anterior end of another worm, 
leaving posterior end of piece exposed. This has begun to regenerate. E. After Hazen. 
Similar experiment in which a new head regenerated at posterior end of grafted piece. 
F. Two longer pieces of A.fxtida united by anterior ends. One end was subsequently cut 
off and a new tail regenerated. G. End of a developing piece of Tubularia mesefnbryanthe- 
mum that had been cut off; it has regenerated, at its proximal end, another proboscis. 



another tail on the anterior end of the posterior piece. The polarity 
of the new part is in this case reversed, as compared with that of 
the piece from which it arises. In the earthworm there is a marked 
delay in the regeneration of these heteromorphic parts. Even in 
tubularia in which heteromorphosis takes place, there isjjsually, a 

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40 REGENERATION 

delay of twenty-four hours in the formation of the reversed head. 
In Planaria lugubris^ in which a reversed head develops, if a piece is 
cut from the anterior end just behind the eyes, the delay in the for- 
mation of the reversed head is very slight, if indeed there is any 
delay at all. 

In the earthworm and in the planarian the production of reversed 
structures appears to be connected with the part of the body through 
which the cut is made, and to be due to internal factors. The ques- 
tion arises whether the presence of certain organs at the exposed 
surface can account for the result. It is conceivable that if such 
organs are present, and produce new cells that go into the new 
part, the presence of such cells may be the factor that determines 
what the new part will become; and in consequence the polarity 
of the part may be reversed. For example, the presence of the 
cut-end of the oesophagus or of the pharynx at the posterior sur- 
face of the anterior piece of the earthworm may determine that a 
new pharynx develops at the cut-end, and this may in turn act on 
the rest of the new tissues in such a way that a head rather than a 
tail is formed. When a posterior piece is cut off, the presence of the 
stomach-intestine at the cut-end may influence the new part, so that a 
tail is produced. It can be shown, however, that a new head may 
arise at the anterior end of a piece that contains only the stomach- 
intestine, as sometimes occurs when the worm is cut in two anterior 
to the middle ; and it is not improbable that a tail can be produced 
from the posterior end of a piece that contains the old oesophagus, 
and perhaps even the old pharynx. In the planarian I have espe- 
cially examined this point, but I have not yet found that the result 
can be referred to the cut-surface passing through any particular 
organ, or to the absence of any organs at the cut-end. 

If, instead of referring the result to any one organ, we assume that 
the tissues near the cut-ends are specialized in such a way that they 
can only produce their like, and that the sum total of tissues of this 
sort making up the new part determines the result, we can only sug- 
gest that this may be so, but we cannot show at present that it is so, 
or that the result could be brought about in this way. 

We might make an appeal to the hypothesis of formative stuffs, 
and assume that there are certain substances present in the head, and 
others in the tail, of such a sort that they determine the kind of dif- 
ferentiation of the new part ; but this view meets also with serious 
objections. In the first place, it gives only the appearance of an 
explanation because it assumes both that such stuffs are present, and 
that they can produce the kind of result that is to be explained. 
Until such substances have been found and until it can be shown that 
this kind of action is possible, the stuff-hypothesis adds nothing to 

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the facts themselves, and may withdraw attention from the real solu- 
tion of the problem. 

Bonnet, who first proposed the hypothesis of specific stuffs, went 
further and assumed also that they move in definite directions in the 
body, the head-stuff flowing forward and the tail-stuff flowing back- 
ward. It was necessary to assume definite movements of the stuffs 
in order to account for the development of the head at the anterior 
end of a piece and of a tail at the posterior end. In cases of hetero- 
morphosis of the sort described above, these stuffs, if they brought 
about the results, would have to move in opposite directions from those 
assumed in the hypothesis ; or else that part of the hypothesis that 
postulates the movement of the substances must be dropped, and in its 
place there must be substituted the idea of the excessive amount of 
such substances in the ends accounting for the heteromorphosis. An 
hypothesis that must be changed in this fundamental way to explain 
both classes of facts cannot be given very serious consideration. Of 
these possible ways in which it has been 
attempted to account for the phenomenon 
of heteromorphosis, the first one suggested 
seems to me simpler and more probable, but 
which organs are to be made responsible 
for the result cannot at present be stated. 
The fact that both Bardeen and I have ob- 
tained heteromorphosis in planarians in 
other regions than in the head indicates 
at least that other factors than the presence 
of head tissues or of head substances may 
bring about the development, and if it can 
be discovered what produces the result in 
regions remote from the head we may be 
in a position to explain the result in the 
head region in the same way, although it may 
be, of course, that the same result may be 
brought about by different factors, when the 
internal conditions are somewhat different. 

Another phenomenon connected with 
the polarity of a piece is shown by Ceri- 
antlms membranaceous. When a triangular 
piece is cut from the side of the body, a half 
circle of tentacles appears around the lower 
edge of the cut, as shown in Fig. 15, C, 
The presence of a free distal edge on the 
lower side of the opening is a sufficient 
stimulus to call forth the development of tentacles. 




Fig. 17. — After Voigt. Planarian 
with three oblique cuts at side. 
The most anterior cut (left 
side), directed forward, pro- 
duced a tail. The one on the 
right side, directed backwards, 
produced a head. The most 
posterior cut (left side) made 
a head with pharynx, and also 
a tail-like outgrowth. 



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42 



REGENERATION 



A somewhat similar result is obtained when an incision is made in 
the side of the body of a planarian. A lateral head may grow out 
from the anterior edge of the cut-surface, as shown in Fig. 17. 

It has been shown by Loeb that if the incurrent siphon of the ascid- 
ian Ciona intestinalis be partially cut off, new eye-specks develop 
around the margin of the cut, as shown in Fig. 18, -^. I have repeated 





Fig. 18. — A. After Loeb. Anterior end of Ciona intestinalis with oral-siphon partially cut off. 
Eye-specks regenerate, both on oral and aboral edge. B. Same (after T. H. M.), showing 
similar result on excurrent siphon. 



this experiment and obtained the same result, and found, as had 
Loeb also, that the same holds true for the excurrent siphon (Fig. 
18, B\ In these cases the new eyes appear both on the anterior 
and posterior edges of the cut. Most probably the result is con- 
nected with an external stimulus, rather than with an internal one. 
This may be true also for cerianthus, but probably not for the 
planarian. 



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INTERNAL FACTORS OF REGENERATION IN ANIMALS 43 

LATERAL REGENERATION 

Since the most familiar qases of regeneration are those that take 
place at the anterior and posterior ends, we not unnaturally come to 
think of polarity as a phenomenon connected only with the long 
axis of the animal ; but there are also many cases of lateral regenera- 
tion in which a similar relation can be shown. In such a case as the 
regeneration of the leg of a salamander, or of a crab, we find 
instances of lateral regeneration, but since the development takes 
place in the direction of the long axis of the leg, the polarity of the 
leg may be thought of as substituted for that of the body. In other 
animals, however, the regeneration is strictly lateral. I have found 
that if the anterior end of an earthworm, or even of lumbriculus, is 
split lengthwise in halves, and then one of the half-pieces is removed, 
the missing half is replaced by the half left attached to the rest of 
the worm. Trembley split a hydra lengthwise into two pieces, and 
each piece bent inwards to make a new tubular body. Bickford, 
Driesch, and I have obtained similar results with pieces of the stem 
of tubularia. 

In planarians which have a flat, broad body, lateral regeneration 
takes place readily. If a worm is split in two along the middle line 
of the body (Fig. I3|, A\ each half regenerates the missing half. 
This is brought about by the development of new tissue along the 
cut-side, and the extension into the new part of outgrowths from the 
digestive tract. Lateral regeneration also takes place if the worm 
is split lengthwise into two unequal parts. In this case the larger 
piece produces new material along the cut-side, and into this new 
part the branches of the old digestive tract extend. The smaller 
piece also produces new material along the cut-side, a new pharynx 
appears along the line between the old and the new tissue, and a new 
digestive tract is formed out of the remains of the old one (Fig. 
19, a, b, c). New branches grow out of the fused part into the 
new tissues at the side. The new worm that develops from a piece 
that is less than half the width of the old worm is about as wide as 
the piece that was cut off, for what is gained at the cut-side is lost 
in the old part. The piece loses in length also during regeneration. 
If the new worm is fed, it increases in size, gaining in breadth both 
on the old side, as well as on the new side, and in time it becomes a 
full-grown, symmetrical worm. 

In the formation of the new part in these cases of lateral regenera- 
tion it is not difficult to understand how some of the old organs, as 
the digestive tract, grow out laterally into the new part; but it is 
more difficult to see how longitudinal organs, such as the nerve-cord 
and genital ducts, are formed anew. Bardeen, who has examined the 

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44 REGENERATION 

development of the new nerve-cord in lateral pieces, thinks that the 
new nerve-cord grows backwards in the new part from the brain that 
develops at the anterior end, either out of the old brain, if it, or any 
part of it, is left, or out of the new brain that develops from the 
anterior end of the lateral cord that is present in the piece. What 
takes place in pieces cut so far to one side that none of the old cord 
is present in the piece he did not make out ; but I can state that a 

new brain develops even when none 
of the lateral cord is present. 

The development of a new head 
in pieces cut to one side of the old 
median line offers some facts of 
interest. A piece may be cut from 
the side of a planarian of such a 
shape that it has no anterior sur- 
FiG. 19. ~ Indicating how a piece is cut off f^-ce at all (Fig. 19, A)\ yet a head 
from side of pianaria macuiata. a, b, dcvelops at the anterior end of the 

c. Regeneration of last. a. Regenera- • 1 v u 

tion of single head at side. e. Regenera- new material that appears at the 
tion of two heads at side. ^^^^ j^ ^^^^^^ ^^ ^^^^ ^^ ^^^ ^j j^^ 

later it assumes an anterior position. In this case an axial structure 
arises in a lateral position, unless we look upon the new head as 
arising at the anterior end of the new part, rather than at the side 
of the old, but there is no evidence in favor of such an interpretation, 
since the head arises at the same time as does the rest of the new 
material at the side. In a small piece all of the new material at the 
side may be used to form the new head (Fig. 19, dy Sometimes 
two heads develop (Fig. 19, e\ 

REGENERATION FROM AN OBLIQUE SURFACE 

There are also certain important facts connected with the regen- 
eration from an oblique surface. The first case of the sort was 
described by Barfurth. He found that if the tail of a tadpole is cut 
off obliquely, as shown in Fig. 20, B, the new tail that develops stands 
at first at right angles to the oblique surface. The angle that the 
new tail makes with the axis of the old tail will be in proportion to 
the obliquity of the cut-surface. The notochord that occupies the 
centre of the new tail begins at the end of the old notochord, and 
extends to the tip of the new tail, dividing it in the same proportion- 
ate parts as does the notochord of the normal tail. The other organs 
occupy corresponding positions. As the new tail becomes larger it 
slowly swings around into line with the old part. This phenomenon 
of regeneration from an oblique surface has been found in a number 
of other forms. It has been described by Hescheler, and by myself 



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45 



in earthworms (Fig. 20, D\ both for the anterior and posterior ends. 
I have shown that it also takes place in the tail of a teleostian fish, 
fundulus (Fig. 20, C), and have offered the following explanation of 
the phenomenon. The new material that is first laid down is, to a 
certain extent, indifferent as regards its axes. A symmetrical struc- 




\\ 



, s 





.1 \ 




Fig. ao. — A, A^. After Driesch. A. Piece of stem of tubularia cut off obliquely, showing oblique 
position of tentacles. AK Same, later stage. B. After Barfurth. Tail of tadpole regenerat- 
ing from oblique surface. C. Tail of fundulus regenerating from oblique surface. D. After 
Hescheler. Anterior end of allolobophora regenerating from oblique surface. £. Piece of 
planaria, cut off by two oblique cuts, regenerating new head and tail. F, F^, F^. Three 
stages in the development of a new head (of a piece of bipalium) at anterior end of oblique 
suiface. 

ture is then formed, with the old edge as a basis. The median 
point of the cut-edge connected with the median point of the outer 
surface of the new edge, gives the axis of symmetry of the new tail. 
The other regions assume corresponding positions. In the tail of 
the tadpole the position of the new notochord is determined by the 

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46 



REGENERATION 



cut-end of the old notochord and the median, outer point of the new 
material, and since the new material is at first equally developed 
along the cut-edge, or at least symmetrically developed, the new tail 
must stand at right angles to the cut-edge. This explanation will 
cover, I think, all cases of regeneration from an oblique surface. It 
assumes a law of symmetry in the new material that is in accordance 
with the observed position in which the new structure appears. The 
hypothesis makes no pretence to explain why the new structures 
should assume a symmetrical position, but given that they do, the 
observed result follows. 

There are certain peculiarities connected with the regeneration 
from an oblique surface in planarians that may be considered in this 
connection. If the worm is cut in two by means of an oblique cut, 
as shown by the oblique line in Fig. 21, -ff, the new head that appears 



f^ r\ f\ (^ f^ 





Fig. 21. — Planaria lugubris. Upper row. A. Part of head cut off obliquely ; a-a^. Regenera- 
tion of new head. Lower row. B, More of head cut off obliquely ; b-b^. Regeneration of 



on the anterior cut-surface of the posterior piece appears at one side 
and not in the middle of the oblique surface (Fig. 21, 5, b\ The new 
head stands at right angles to the cut-surface. The anterior piece of 
the worm produces a new tail at the side of the posterior cut-surface^ 
in the same way that the tail is formed in Fig. 20, E. The tail 
also stands at right angles to the cut-surface. The new pharynx 

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that develops in a piece of this kind appears in the middle of the pos- 
terior cut-surface, between the old and the new parts. It may extend 
somewhat obliquely in the new part, and point toward the new tail. 

If a piece is cut from the anterior part of a worm by two oblique 
and parallel cuts, the new head appears at one side of the anterior 
cut-surface, and the new tail at the other side of the posterior cut- 
surface. The new pharynx appears in the new material of the pos- 
terior part in the middle line. Thus the middle lines of the new 
head and tail and pharynx lie in dififerent positions, yet these parts are 







Fig. 93. — Two upper rows Planar ia lugubris. Lower row Planar ia maculata. Upper row. 
Tail-piece cut off obliquely in front of genital pore. Figures show niode of regeneration. 
Middle row. Piece including old pharynx cut off by two cross-cuts, regenerating head and 
taiL Lower row. Piece cut off as last, regenerating head and tail. ' 

subsequently brought into the same line. This is done by the head ex- 
tending more forward and becoming broader, the tail growing backward 
and also becoming broader. The old piece becomes narrower at the 
same time. These three changes going on simultaneously produce a 
new symmetrical worm. In one form, Planaria lugtibris, the symmetri- 
cal form is reached largely by the forward growth and the enlargement 
of the head, and the growth backward and the enlargement of the 
tail (Fig. 22, B). In Planaria tnacidata the old part shifts, so that it 
forms a new median line connecting the median line of the new head 

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48 REGENERATION 

and new tail. This is best shown when the piece includes the old 
pharynx (Fig. 22, C). The pharynx is also shifted, so that its anterior 
end points towards the side at which the new head lies, and its pos- 
terior end towards the new tail. The result is that a new symmetri- 
cal worm is formed, as shown by the series of figures in Fig. 22, C. 
In Planaria maculata the changes take place largely in the old part, 
and the old material extends throughout the entire length of the new 
worm. In Planaria liigiibris the change takes place largely in the 
new parts (Fig. 22, B). The general method in the latter species by 
which the symmetry is attained can be best shown by cutting the 
worm in two by an oblique cut just in front of the genital pore (Fig. 
22 f A), The posterior piece produces a new head at the side, and a 
new pharynx appears along the border between the new and the old 
parts, as shown in these figures. Its posterior end touches the middle 
line of the old part, and from this point it extends obliquely across 
the new tissue towards the middle of the new head. As regenera- 
tion goes on the new head is carried farther forward, it becomes 
larger, and the main region of new growth is found to be, in the fig- 
ure, to the left side of the new part. As a result of these changes the 
new head turns forward, and comes to lie nearer the middle line of 
the old part. The pharynx is also turned more forward, and finally, 
as the new parts enlarge, the symmetrical form is produced. The 
internal factors that are involved in the development of these oblique 
pieces are very difficult to analyze. The position of the new head 
and tail at one side of the cut-edge is the most difficult phenomenon 
of all to explain. We may, I think, safely regard the first new mate- 
rial that is proliferated along the cut-edge as totipotent, and our spe- 
cial problem resolves itself into discovering what factor or factors 
determine that the new head is to form at the most anterior end of 
the new material, and the new tail at the most posterior end. If we 
assume that the result is in some way connected with the influence 
of the old part on the new, and that this influence is of such a sort 
that the more anterior part of the old tissue determines that one side 
of the head must be at the most anterior edge, we have at least a 
formal explanation of the position of the head at the side. Given the 
position of the new head fixed at one side, its breadth will be determined 
by the maximum breadth possible for the formation of a new head. 
This is also in part an assumption, but it has at least certain general 
facts of observation in its favor. The oblique position of the new 
head is the result of its symmetrical development in the new material 
in the same way that the position of the tail of the fish or of the tad- 
pole is the result of the symmetrical formation of the new tail on the 
oblique surface. The subsequent changes, by means of which a sym- 
metrical worm is developed, are the result of different rates of growth 

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INTERNAL FACTORS OF REGENERATION IN ANIMALS 49 

in the different parts. In this connection the most important fact is 
that the growth takes place most rapidly where it will bring about the 
new form. This problem, which is one of the most fundamental in 
connection with the phenomena of development and of regeneration, 
will be more fully discussed in a later chapter. 

A number of assumptions have been made in the above attempt to 
give an analysis of the formation of a head at the side of an oblique 
surface. That these assumptions are not entirely arbitrary, but have 
a certain amount of evidence in their favor, can, I think, be shown. 
The new material that first appears is supposed to be totipotent, in 
the sense that any part of it may produce any part of the structure 
that develops from this material. That this is probable is shown by 
the following experiment. If a cross-piece is cut from a worm, and 
then split lengthwise into halves, each half will produce a new head 
at the anterior edge of the piece. This result shows, at least, that 
from the tissue lying to the right or to the left of the middle line new 
material may be formed from which a whole head may develop. The 
new head does not stand at first with its middle axis in line with the 
middle of the old piece, ue. it does not stand squarely at the anterior 
end of the half-piece, but more towards the inner side of the piece. 
It may appear that the old part has sufficient influence on the new 
part to shift the axis of the latter toward the old middle line, but 
while some such influence may be present, it is probable that the posi- 
tion of the head is in part the outcome of another factor, viz. the 
presence at the inner side of the piece of an undeveloped new side, 
with which the explanation of the less development of the inner side 
of the head is also connected. 

If a cross-piece is cut from a worm and kept until a small amount 
of new tissue appears over the anterior and posterior cut-surfaces, 
and if then the piece is split in two lengthwise, there will develop 
from each piece a new head out of the new material over the anterior 
surface. The result shows ^ /\ 




I/- 



that the new material is at 
first totipotent, in the sense 
that it may still produce 
one or more heads accord- 
ing to the conditions. It Yl0.^z,--Planariamaculata, ^. Cross-piece. alWd to 
is possible, of course, that regenerate, then cut in two lengthwise, as indicated by 

^, - ^ r ^t line. a-a*. Regeneration of left half. 

the formation of the new 

head may have begun at the time of the experiment, but if it had, 
the development had not gone so far that a new arrangement was 
impossible. If, however, the piece is not cut lengthwise until just 
before the formation of a head (Fig. 23, A\ then each half-piece pro- 
duces at first a half-head, that completes itself later at the cut-side. 

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REGENERATION 



Another experiment shows even more satisfactorily that the 
material over an anterior cut-edge may produce one or more new heads 
according to the conditions, and that the result is not connected with 
the region from which the new material is derived. If the anterior 
end of a planarian is cut off and then an oblong piece is removed from 
the middle of the worm, as shown in Fig. 24, A, it will be found, if 





Fig. 24. — Planaria lugubris, A. Showing where a piece, 4, was removed from middle of a 
worm, a, b. Regeneration of a single head, c, cK Regeneration of two heads. £>, £, F. He- 
generation of small piece, 4, that was cut out 

the side parts are kept from fusing together in the middle line, that a 
new head develops at the anterior end of each part, as shown in Fig. 
24, c, c^. If, on the other hand, the two sides come together and fuse 
in the middle line, as shown in Fig. 24, a, b, the new material that 
appears over their anterior ends becomes continuous and produces 
a single head. In this case, although the middle part of the old 
tissue has been removed, a single head develops that is normal in all 
respects, and the eyes are not nearer together than when the middle 
part is present, as when regeneration takes place from an anterior 
cross-cut surface. 

The assumption that the lateral position of the head on an oblique 
surface is connected with the more anterior region of the old material 
that is found at that side, can be made at least more intelligible by 
the following experiment: If the head of a planarian is cut off 
obliquely, as indicated in Fig. 21, ^, so that one of the "ears*' is left 
at one side, the new head arises at the side in connection with the 
part of the old head that lies at that side. The new head does not 
extend over the entire cut-surface, which is longer of course than a 
cross-cut would be, but lies at one side, as in the other cases just 
described. In this case we can see that if the new head cannot, on 
account of certain conditions, extend over the entire cut-surface, one 
side of it may be determined by the presence of a part of the old head. 

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INTERNAL FACTORS OF REGENERATION IN ANIMALS $1 

and this influence may be stronger than any other that might tend 
to locate the new head in the original middle line. If we suppose 
that similar conditions prevail in all cases when oblique surfaces are 
present in these worms, we have a formal solution of the problem. 
The argument cannot be convincing unless we can give a further 
explanation of the nature of this influence that the old part has upon 
the new. 

In other cases, as in the regeneration from an oblique surface in 
the tail of the tadpole and of a fish, we must assume that the factor 
that determines the middle of the new part has a stronger influence 
on the new material than has the most posterior part of the old 
tissue. 

The influence of an. oblique cut-surface on the position of the 
new parts is shown in a different way in the hydroid, tubularia. 
The conditions are different in this case inasmuch as there is no 
proliferation from the cut-end, but the old part produces the new 
hydranth. Driesch found that if the stem of tubularia is cut in 
two obliquely, the new tentacles, that develop as two rings around 
the tube near its cut-end, stand obliquely on the stem,^ as shown in 
Fig. 20, A, In most cases, both the distal and the proximal circles 
of tentacles lie obliquely to the long axis of the stem, but there is 
some variability in the result, and occasionally one or the other, 
especially the proximal circle, may be squarely placed, although, as 
a rule, the influence of the oblique cut-end can be seen. It can be 
shown, I think, that the oblique position of the rings of tentacles in 
tubularia is the outcome of factors different from those that are 
found in the regeneration of the tail of the tadpole and of the head 
and tail of the planarian. Driesch suggested that the distance of 
the tentacle-rings from the cut-end is the result of some sort of 
** regulation *' that determines their position at a given distance from 
the region at which the surrounding water acts on the exposed end. 
Hence, if the exposed surface is an oblique one the rings will also 
be formed in an oblique position. On the other hand, I have sug- 
gested that we can imagine the regulation to result from other 
factors. At the beginning of the development, and before the 
tentacles appear, there is a withdrawal of tissue from the cut-end 
that leaves the region from which the proboscis develops quite thin. 
If this material withdraws at a uniform rate and to the same distance 
at all points from the end of the piece, as observation shows to be 
the case, and if, as appears also to be true, the outer end of the distal 
ring of tentacles lies at the inner end of the proboscis region, then 
it too will assume an oblique position if the cut-end is oblique. If 
we imagine a similar series of regulations taking place throughout 

^ The same holds good for the basal hydranth if it arises near an ()l)lique em). t 

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52 



REGENERATION 







Fig. 25. — Piece of stem of Tubularia nusembry- 
anikemum split in two lengthwise. Forma- 
tion of whole hydranth that turned away 
from contact with old perisarc. 



the piece, we can account for the 
results. On this hypothesis the 
action of the water on the free 
end need not be a factor in the 
result, but the oblique end is itself 
sufficient to determine the series 
of regulations, or mass-relations, 
that lead to the laying down of 
an oblique hydranth. 

When the hydranth protrudes 
from the stem it assumes an 
oblique position, as shown in Fig. 
20, A^. Driesch supposed the 
oblique position of the hydranth 
to be due to an oblique zone that 
develops behind the hydranth, but 
the result can best be explained, 
as certain other experiments that 
I have made seem to show, as 
due to the negative thigmotropism 
of the hydranth at the time it pro- 
trudes from the old perisarc. It 
turns away from the projecting 
side of the oblique end of the 
perisarc, as it does from any solid 
body with which it comes in con- 
tact. That this is the case is best 
shown by splitting the stem length- 
wise into halves. In this case, 
although the two circles of ten- 
tacles may be laid down squarely 
(Fig. 25, A\ the new hydranth 
protrudes at right angles to the 
old perisarc, as shown in Fig. 
25. B, 



THE INFLUENCE OF INTERNAL ORGANS AT THE CUT-SURFACE 
ON THE NEW STRUCTURE 

In a few cases it has been discovered that the presence of certain 
organs at the exposed surface is necessary in order that regenera- 
tion may take place. The following experiment that I have recently 
carried out shows, for instance, the influence of the nerve-cord on 
the regenerating part. A fe\7 of the anterior segments of the earth- 
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INTERNAL FACTORS OF REGENERATION IN ANIMALS 



53 





=' 



B 




B 



worm are cut off, as shown in the left-hand figure in Fig. 26, and 
then a piece of the mid-ventral body wall of the worm is cut out, 
a part of the ventral nerve-cord being removed with the piece. The 
cut-edges meet along the mid-ventral line and fuse, closing the 
wound. As a result of the operation there is left exposed, at 
the anterior end of the worm, a cut-surface with all of the internal 
organs present except the nervous system. The anterior end heals 
over, but I have not observed the development of a new head at this 
level, although the exposed end is in a region at which, under 
ordinary circumstances, a new head readily regenerates. In several 
cases a new head developed at the 
point where the cut-end of the ner- 
vous system is situated, i.e. at the 
level B in the figure. 

A variation of the same experi- 
ment shows still more conclusively 
the importance of the nervous sys- 
tem for the result. A few anterior 
segments are cut from the anterior 
end as before. A cut is made, as 
shown in the right-hand figure in 
Fig. 26, to one side of the mid-ventral 
line (indicated by the black line in 
the figure at the level A). Then, at 
the posterior end of this cut a piece 
is removed from the mid-ventral 
line as in the former experiment 
(shown by the stippled area in the 
figure). A portion of the ventral 
nerve-cord is removed with the piece. 
As a result of this operation, two 
anterior ends of the nervous system 
are left exposed (shown by the black 
dots in the figure). At the anterior 
end of the worm, i.e. at A^ there is 
one exposure, and at the posterior 
end of the region from which the 
piece was removed there is another. 
Two heads develop in successful 
cases, one at the anterior end of the anterior cut-surface, i.e. at A^ 
and the other at B. 

The results show that in the absence of the cut-end of the nervous 
system at an exposed surface a new head does not develop ; and con- 
versely, the development of a new head takes place when the anterior 

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_ 



^ 

-- 



^ 



^ 



h 



J 



Fig. 26.— I^ft-hand figure X 8ho\\s how, 
alter cutting oft' the anterior end of A//0/0- 
bophora fatida, a piece of the ventLil 
wall (including a part of the nerve-cord) 
is cut out. Right-hand figure Y illus- 
trates a more complicated operation, in 
which the piece of the ventral wall that 
is cut out is a little behind the anterior 
end. 



54 REGENERATION 

end of the nervous system is present at a cut-surface, even when such 
a surface is not at the anterior end of the worm. We may perhaps be 
able to extend this statement, and state that as many heads will 
develop as there are exposed anterior ends of the nervous system. 

In two other cases, at least, a somewhat similar conclusion may be 
drawn, although it appears that in these cases other organs than the 
nervous system may be the centres around which the new parts 
develop. Tomier has shown that when the vertebrae of the tail of 
the lizard are injured, the new material proliferated by the wounded 
surfaces serve as centres* for the regeneration of new tails; and 
Barfurth has found that the notochord in the tail of the tadpole plays 
a similar r61e in the formation of a new. tail. These experiments will 
be more fully described in connection with the formation of double 
structures, but from what has been said it will be seen that the cases 
are parallel to that of the earthworm. 

Until more has been discovered in regard to the internal factors of 
regeneration, it would be venturesome to make any general statement 
based on these few cases, but there is opened here a wide field for 
experimental work. By eliminating one by one the different organs 
that are present in the old part, it may be possible to discover much 
more in regard to the internal conditions that are necessary in order 
that the process of regeneration may take place. 

THE INFLUENCE OF THE AMOUNT OF NEW MATERIAL 

There are certain results connected with the amount of new mate- 
rial which is produced during regeneration, that should be considered 
in connection with the question of internal factors. It has been 
pointed out that when one segment only is removed from the ante- 
rior end of the earthworm only one new one returns ; when two 
are cut off two come back, and this holds good up to five segments. 
Beyond this, no matter how many are removed, only five at most come 
back. The latter result seems to be connected with the amount of 
material that is formed over the cut-surface before differentiation 
begins. When only one or two segments have been cut off, the new 
material that is formed is soon sufficient in amount for the production 
of one or two new segments, but when three to five are cut off some- 
what more material is formed before differentiation begins. When 
more than five are cut off the new material is at best only sufficient 
to produce five new ones, and in some cases even a smaller num- 
ber is formed. This hypothesis assumes that there is a lower limit 
of size for the formation of new segments below which a segment 

1 Although it is by no means certain that the results may not be due in part, at least, to 
injuries to the nervous system. 



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A 
INTERNAL FACl^ORS OF REGENERATION IN ANIMALS 55 

cannot develop. The interpretation is fully in accordance with what 
we know to be the case for small pieces of hydra and of other forms 
that, below a certain minimal size, do not regenerate. The question 
as to how many segments are formed out of the new part is determined, 
not only by the amount of new material, but also by the number of 
segments to be replaced, at least up to five segments. Beyond this 
limit we may think of the maximum possible number of segments 
appearing in the new material. That a relation of some sort obtains 
between the old and the new parts, that may have an influence 
on the number of the new segments which are formed, is shown by the 
fact that, when one, two, three, four, or five are cut off, just this 
number comes back. A sort of completing principle exists as a 
factor in the result, but when so much has been cut off that the old 
part cannot complete itself in the new material that is formed, then 
other factors must determine how many segments will be produced. 

In planarians we find a similar phenomenon. If much of the 
anterior end is cut off, only a head is formed at the anterior cut- 
surface of the posterior piece, and the intermediate region is 
absent. I interpret this in the same way as the similar case in the 
earthworm. As soon as enough new material has been formed 
for the anterior end to appear, it begins to develop, and since it can- 
not develop below a certain minimal size, or rather, since the ten- 
dency to produce a head approaching the maximum size is stronger 
than the tendency to produce as much as possible of the missing 
anterior end, all the new material goes into the new head. In the 
planarian the possibility of subsequently replacing the missing region 
behind the head exists, and the intermediate part is later pro- 
duced, the head being carried farther forward. The same is true of 
the new posterior end of the earthworm, in which a growing region 
is established at a very early stage in front of the tip of the tail, 
but no such growing region is present at the anterior end in the 
earthworm. These differences appear to be connected with the 
general phenomena of growth in these forms. In the planarian 
interstitial growth can take place in any part of the body, hence the 
possibility of producing a missing region is present in all parts of 
the worm ; but in the earthworm we never find new segments inter- 
calated at the apteribr end during normal growth, nor does this 
take place during regeneration. At the posterior end of the earth- 
worm we find a region of growth in which new segments are pro- 
duced, and we find the same thing is true in the regeneration of the 
posterior end. In other words, the growing region in front of the 
last segment is also regenerated. 

It has been found in several forms that pieces below a certain size 
do not regenerate. In those cases in which a small piece ilies soon 

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S6 REGENERATION 

after its removal from the rest of the body we have no direct means 
of knowing whether or not the piece has potentially the power to 
regenerate, but in some other cases, in which small pieces may be 
kept alive for some time, they may not regenerate. Furthermore, 
the regeneration of small pieces that are just above the minimal size 
is often delayed and is sometimes imperfect. These small pieces 
seem to meet with a greater difficulty in regenerating than do larger 
pieces. Peebles has shown that pieces of hydra that measure less 
than \ mm. in diameter (= about ^^^ of the volume of hydra) do not 
regenerate, although if very small pieces are taken from a develop- 
ing bud they may regenerate, even when only \ mm. in diameter. 
Very small pieces that are, however, just above the minimal size, 
while they may assume a hydra-like form, produce only one or two 
tentacles. The failure of the smallest pieces to regenerate is not 
due to their dying, since they may live for a much longer time than 
would suffice for larger pieces to regenerate. Isolated tentacles of 
hydra do not produce new hydras, although they may remain alive 
for some time. A single tentacle is larger than the minimal piece, 
so that its failure to regenerate is probably connected with the differ- 
entiation of the tentacle, rather than with its size. The lack of 
power to regenerate in .the smallest pieces of hydra cannot be con- 
nected with the absence of any special organ, 
since these pieces contain both ectoderm and 
endoderm. In tubularia also, Driesch and 
I have found that pieces below a certain size 
do not regenerate (Fig. 27). There is likewise 
in planarians a lower limit of regeneration, 
even for pieces that contain all the ele- 
ments which, being present in larger pieces, 
make regeneration possible. Lillie has found 
(J D that nucleated pieces of the protozoon stentor 

Fig. 27.— Tubularia mesembry- fail to regenerate if they are below the mini- 
^^tTh^t p;odir^^^^^^^ malsize. He places this minimal size at 80 ^ 
dranth. B, c. Pieces below diameter, which he calculates as ^V of the 

minimal size. D, Ring pro- r » r i • , , 

duced by closing of small volume of the stcntor from which the piece 
P*®^*^" has come. I have obtained a slightly smaller 

piece that regenerated, and since it came from a larger stentor it repre- 
sents about ^j of the whole animal. The lack of the power of devel- 
opment of these smallest pieces seems to be due to the absence of 
sufficient material for the production of the typical form. We can 
give no other explanation of the phenomenon at present, especially 
since the pieces contain material that we know from other experiments 
has the power of producing any part of the organism. The super- 
ficial area of small pieces is relatively greater than that of larger pieces, 

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INTERNAL FACTORS OF REGENERATION IN ANIMALS* 57 

but there is no evidence that this relation can in any way influence 
the result. Whether the difference in surface tension could prevent 
the small piece from assuming the typical form and hold it, as it 
were, in a spherical form is not known, but there is little probability 
that this is the explanation of the phenomena. 

The regeneration of small pieces of animals and of plants may 
often fail to take place, because, as Vochting has pointed out, the 
injury caused by the cutting may extend so far into the small piece 
that its repair may be impossible. In other cases there may be an 
insufficient reserve supply of food stuff, although, if a proportionate 
form of any size could be produced, it is difficult to see how this could 
be the case. There can be no doubt, however, that pieces taken from 
parts of the body that are dependent on other parts for their food, 
oxygen, etc., will die for lack of these things, and even if they can 
live for some time their further development may not take place in the 
absence of sufficient food to carry on the process. After these pos- 
sibilities have been given due weight, there remain several cases in 
which there can be little doubt that the failure of a small piece to 
regenerate is owing to the lack of sufficient material to produce even 
the smallest possible form for that sort of material, i,e, for the organ- 
ization to be formed on so small a scale. 

There are some facts in connection with the regeneration of small 
pieces of tubularia that have an important bearing on this question of 
organization size. If long pieces of the stem are cut off, the new 
hydranth, that develops out of the old tissue at the end of the piece, 
occupies, within certain limits, a region of definite length. If pieces 
of the stem are cut off that are only twice the length of the hydranth- 
forming region, the length of the latter will be reduced to half the 
length that it has in longer pieces, and if still smaller pieces are cut 
off, the hydranth-forming region may be reduced, as Driesch has 
shown, to seventy per cent of the normal length. The hydranths 
that develop from the smaller pieces have also a reduced number of 
tentacles, as I have found. It was first shown by Bickford, and later 
by Driesch, and by myself, that in many cases very short pieces of 
the stem of tubularia produce only the distal parts of a hydranth. 
This happens most often when the length of the piece is less than 
the average normal length of the hydranth-forming area, but it may 
also take place in pieces that are much longer than the minimal size 
of the least hydranth-forming region. Driesch made the further dis- 
covery, which I have confirmed, that pieces from the distal end of the 
stem are more likely to produce these partial structures than are 
pieces from the more proximal part. Some of these partial structures 
are represented in Fig. 28, C-G. Sometimes the inner tube, or coeno- 
sarc, which is composed of the two layers of the body, ectoderm and 

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58 



REGENERATION 



endoderm, draws away from the chitinous perisarc, as shown in Fig. 
28, B, A hydranth with a short stalk is then produced. In other cases, 
Fig. 28, C, almost all of the coenosarc is used up to form the hydranth, 
and only a short, dome-shaped knob represents the stalk. In still other 
cases there may be no stalk at all (Fig. 27, D\ but only the hydranth. 
Forms like the last two are more often produced from pieces of the 




Fig. 28. — Tubularia mesembryanfhemum. Products of regeneration of short pieces. A. Piece 
that regenerated a hydranth in same way as do longer pieces, but with fewer tentacles. 
B. Pieces whose stem drew away from wall of old perisarc (cylinder in figures). C. Hydranth 
with almost no stalk. D. Hvdranth without stalk. E. Distal part of hydranth with one long 
proximal tentacle, ^i. Similar, but more reduced. E^. Similar, with'two tentacles at side. 
F, Proboscis with reproductive organs. G, Proboscis without reproductive organs. 

distal end of the stalk. From very small pieces, forms like those shown 
in Figs. 28, E-E^y that represent only proboscides with a reduced 
number of tentacles, are sometimes formed. Reproductive organs 
may be present at the base of these pieces. A further reduction is 
shown in Figs. 28, F, G, that are proboscides with only the distal circle 
of tentacles ; in one of these, reproductive organs are present around 
the base. Partial forms more reduced than these have not been found. 



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INTERNAL FACTORS OF REGENERATION IN ANIMALS 59 

If we examine the factors that determine the production of the 
partial structures, we find, in the first place, that the size of the piece 
is of the greatest importance. The reduced forms appear most often 
in pieces that are shorter than the average length 'of the hydranth- 
forming area. A second factor is connected with the region of the 
stem from which the piece is taken. Larger pieces from the distal 
end produce partial structures, especially hydranths with very short 
stalks (Fig. 28, C\ or with none at all (Fig. 28, D\ There are cer- 
tain facts connected with this distal region, which lies just behind the 
hydranth, that should be mentioned in this connection. It was first 
discovered by Dalyell that a hydranth-head lives for only a limited time, 
and that when it dies a new head is regenerated from the region behind 
the old one. The stalk of the new hydranth continues to elongate for 
some time after the new hydranth has been formed. Whether this 
continuous growth in the distal end, or the normal formation of a new 
hydranth by it from time to time, can in any way be connected with 
the development of partial structures from this region cannot at 
present be stated. The distal part of the stem contains more of the 
red-pigment, that gives color to the stem and to the hydranth, than 
does any other part. Loeb first advanced the view that the red- 
pigment in the stem acts as a formative substance in Sachs' sense, 
and determines the production of a new hydranth by accumulating 
near the cut-end of the piece. Driesch also assumes the red-pigment 
to be a factor in the result, but supposes that it acts quantitatively, 
rather than in determining the quality of the result. If this red-pig- 
ment acted in the way supposed either by Loeb or by Driesch, it might 
act as one of the factors in the production of these partial structures. 
This red-pigment is contained in the form of reddish granules in the 
cells of the endoderm. The granules are of various sizes, the largest 
being easily seen even with low powers of the microscope. When a 
piece of the stem is cut off, the ends close by the drawing in of the 
cut-edges over the open-end. A circulation of the fluid contained in 
the piece then begins. In the fluid, globules appear very soon that 
contain red-pigment granules like those in the endoderm. The glob- 
ules appear to be endodermal cells, or parts of cells, that are set free 
in the central cavity. The circulation continues for about twenty- 
four hours. At about this time one end of the stem becomes reddish, 
owing to the presence in it of a larger number of red-pigment granules 
than before. The ridges that are the rudiments of the tentacles appear 
(Fig. 30, A\ and a new hydranth very rapidly develops. At the time 
when the hydranth begins to appear the globules in the circulating 
fluid disappear. They disappear at the time when the red-pigment 
of the forming hydranth is rapidly increasing in quantity, and not 
unnaturally one might suppose that the pigment of the circulating 

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6o REGENERATION 

fluid had been added to the wall where the hydranth is produced. 
The globules disappear in the region of the new hydranth, but, I 
think, it can be shown that they do not form any essential part of the 
hydranth. They may be found stuck together in a ball that lies in the 
digestive tract of the new hydranth, and when the hydranth is fully 
formed the pigment is ejected, as Stevens has shown, through the 
mouth. 

The development of the new hydranth begins several hours be- 
fore the red-pigment globules have disappeared from the circulation. 
The walls in the region of the future hydranth begin to thicken, 
and, later, pigment develops in the endoderm of this region. The 
new pigment is formed in the new cells of the endoderm, and does 
not come from the circulating globules, as shown by the development 
of very short pieces of the stem. In these the amount of new pig- 
ment that develops in the new hydranth may be far greater than that 
in the whole original piece (Fig. 30, D\ and in this case there can be 
no question but that new pigment is made in the endodermal cells of 
the hydranth. The formation of a hydranth, that usually takes place 
after another twenty-four hours, from the basal end of a long piece, 
shows that a hydranth may develop when there are no granules in 
the circulating fluid. These basal hydranths may contain as much 
pigment as do the distal ones. 

Driesch suggested that the red-pigment in the circulating fluid 
determines quantitatively by its presence how much of a hydranth 
is formed, or the size of the hydranth in relation to the rest of 
the piece. There seems to be no evidence in favor of this view 
and much against it. Loeb has not stated specifically whether 
he means that it is the pigment in the circulating fluid or that 
in the walls which acts as a formative stuff; the presumption is 
that he meant the latter. An examination of the piece during regen- 
eration gives no evidence in favor of the view that the pigment moves 
into the region of the new hydranth. On the contrary, it remains 
constant in amount at all points except where the new hydranth is 
developing, and there is in this region unquestionably a large develop- 
ment of new pigment. 

The evidence for and against the idea that the red-pigment of 
tubularia is a formative stuff, or even building material, has been 
considered at some length, because it is the only case in which the 
hypothetical formative stuff has been definitely located in a specific, 
recognizable substance that can be followed during the process of 
regeneration. It is well, I think, to give the question full considera- 
tion, especially as the hypothesis often appears to give an easy solu- 
tion of some of the problems of regeneration. In a later chapter the 
subject will be more fully treated. 

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INTERNAL FACTORS OF REGENERATION IN ANIMALS 



6l 



Since the red-pigment hypothesis does not explain the phenomenon 
of the formation of the partial structures in tubularia, we must look 
for another explanation. As the matter stands at present we can only 
assume that there is a predisposition of a very small piece to form a 
larger partial structure than a smaller whole one. This problem of the 
method of development of small pieces of the stem of tubularia is fur- 
ther complicated by the development in many cases of double hy- 
dranths, or double parts of hydranths, as shown in Fig. 29, A-E, 




Fig. 29. — Tubularia mesembryanthemuvn. A, Short piece with hydranth at each end. B, Double 
piece with one circle of proximal tentacles. C. Double piece with only two proximal tentacles. 
D, Double proboscis with two sets of reproductive organs. E-E^. Double proboscis. 

The first form (Fig. 29, A) shows two hydranths turned in opposite 
directions, that are united at their bases. Another form has only a 
single circle of proximal tentacles between the two proboscides (Fig. 
29, B-C). In other forms there are only two proboscides, each with its 
reproductive organs (Fig. 29, Z>), and often there are simply two pro- 
boscides united at the base (Fig. 29, E-E^), It is the rule, even 
in longer pieces, that a hydranth appears at each end of the piece, if 
the piece is suspended or even lies on the bottom of the w^ter ; biit 

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62 



REGENERATION 



in all these cases the basal hydranth develops about twenty-four hours 
after the apical one. In the short pieces, however, the two ends 
develop at the same time, although the development of all the short 
pieces, whatever structures they may produce, whether single or 
double, is delayed, and the hydranths may not appear until after the 
long pieces have produced their basal hydranths. In these double 



Hill 
tllll 



n 



%V 






.i%\ 





B 

Fig. 30. — Tubularia nusembryanthemum, A. Short piece with reduced hydranth-region. B, Piece 
from distal end of stalk producing a hydranth without a stalk (see Fig. 27, D). C Piece pro- 
ducing hydranth as outgrowth of end. Ci. Later stage of last, Z>. Short piece producing 
double proboscis (see Fig. 28, E), 

> structures both ends develop at the same time (Fig. 30, D). If we 
suppose the influences that start the development of the piece begin 
first at the distal end, the region affected will lie so near to the 
proximal end of the piece that the development at this end may be 
hastened, and under these circumstances the region of new forma- 
tion will be shared by the two hydranths. The factors that deter- 
mine that a larger, partial structure is formed in preference to a 
smaller whole one will no doubt be found to be the same in these 
double structures and in the single ones. 



THE INFLUENCE OF THE OLD PARTS ON THE NEW 

One of the most striking and general facts connected with the phe- 
nomenon of regeneration is that the new part that is built up on the 
exposed surface is like the part removed. This suggests that an in- 
fluence of some sort starts from the old part and changes the part 
immediately in contact with it into a structure that completes the old 
part in that region. We can imagine that the new part that has been 
changed in this way may act on the new part just beyond it, and so 
step by step the new part may be differentiated. It is not difficult to 
show that the phenomenon is really more complicated than this, and 
that other factors are also acting on the new part; but, nevertheless, 
that the old part has some such influence is probable. Under certain 
conditions, however, this influence may be counteracted by^ other iac- 

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INTERNAL FACTORS OF REGENERATION IN ANIMALS 63 

tors, and something different from the part removed may be formed. 
One example of this sort has already been discussed, namely, that in 
which after the removal of much of the anterior end of the earthworm 
or of a planarian, only the distal end comes back. Another case is 
that in which something different from the part removed is regener- 
ated. If the tip of the eye of the hermit-crab or of other crustaceans 
is cut off a new eye is regenerated, but if the eye-stalk is cut off near 
its base an antenna-like organ develops. Herbst has suggested that 
the presence of the ganglion at the end of the stalk accounts for the 
regeneration of a new eye, when only the tip of the stalk is cut off. 
In the absence of the ganglion at the cut-edge the stalk does not pro- 
duce an eye, but an antenna, as is shown when the eye-stalk is cut 
off near the base. The factors that determine the development of an 
antenna instead of an eye have not been discovered. Przibram has 
shown that when the third maxilliped of portunas, carcinas, or of other 
crustaceans is cut off near the base, the new appendage that develops 
is different from the one removed, and resembles a leg in many ways, 
but if the animal is kept until it has moulted several times the 
appendage becomes more and more like the part removed. Another 
remarkable case has also been described by Przibram for Alphetis 
platyrrhynchus. In this decapod, the claws of the first pair of legs are 
different from each other, one being much larger than the other and 
having a different structure.^ If the larger claw is thrown off at its 
breaking-joint, and the smaller one left intact, the latter at the next 
moult (or sometimes after two moults) changes into the character- 
istic larger claw and the newly regenerated claw is like the smaller 
one. If the experiment is repeated on this same animal, i,e, if the 
newly acquired large claw is removed, then at the next moult the 
smaller claw becomes the larger one and the new claw becomes 
the smaller one — the conditions now being the same once more as at 
the beginning. If both claws of an animal are thrown off at the 
same time, two new claws regenerate that are both of the same size, 
and each is a small copy of the claw that was removed. As yet no 
experiments have been made that show what factors regulate the 
development of each kind of claw. 

Returning again to the question of the regeneration of parts simi- 
lar to the ones removed, there are some interesting results that Peebles 
has obtained in the colonial hydroids, podocoryne and hydractinia. 
These colonies consist of three principal sorts of individuals : the 
nutritive, the reproductive, and the protective zooids. Peebles has 
found that if the stalks of these zooids are cut into pieces, each pro- 
duces the same kind of zooid as was originally carried by that stalk. 
Pieces of the stem of the nutritive zooid produce new nutritive zooids 

1 In normal animals some have the right claw the larger and some the left. 

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64 REGENERATION 

at the anterior end of the piece, and sometimes also at the basal end. 
A similar statement may be made for each of the other kinds. 
Another method of regeneration sometimes takes place, when, for 
instance, a piece of the stalk of a nutritive individual is left undis- 
turbed without being supplied with fresh water. It sends out root- 
like stolons instead of producing a new zooid. The stolons appear 
first at the ends of the piece, but may later also appear at several 
points along the piece. They make a delicate network, and the origi- 
nal piece may entirely disappear in the stolons. After several days 
new feeding zooids grow out at right angles to the stolon network. 
Pieces of the stalk of protective zooids may also produce stolons, but 
they spread less slowly, and the formation of new individuals was not 
observed. In one case a piece of a reproductive zooid made a short 
stolon, and from it arose a new individual that seemed to be a nutri- 
tive zooid. If the latter result proves to be true, we see that a piece 
may produce a new part that is of a different kind from that of which 
the piece itself was once a part, but this is brought about by the forma- 
tion of a stolon that is itself one of the characteristic structures by 
means of which these colonial forms produce new nutritive zooids. 
In this case there is a return of the piece to a simpler form, the stolon, 
and, acting on this, the factors that produce nutritive zooids may bring 
about new nutritive zooids. The influence of the old structure is lost 
when the piece assumes a new character. 

Another series of experiments gives an insight into an internal 
factor of regeneration that may prove, I think, to be one of some 
importance and help in interpreting certain phenomena. If the 
head-end of a planarian is cut off, the posterior piece split along 
the middle line, and one side cut off, just above the lower end of the 
longitudinal cut, as shown in Fig. 31, yl, it will be found that, if the 
long and the short sides are kept from uniting along the middle 
line, each half will produce a new head on its anterior surface (Fig. 
31, C). If the two halves grow together, and the anterior surface of 
the shorter piece becomes connected with the anterior surface of the 
longer piece by means of the new tissue that develops along the 
inner side of the latter (Fig. 30, B\ then a head appears only 
on the anterior half. The development of a head on the shorter 
half is prevented by the establishment of a connection with the 
new side. Sometimes an abortive attempt to produce a head is 
made, but the posterior surface fails to produce anything more than 
a pointed outgrowth. If we attempt to picture to ourselves how this 
influence of the new side on the posterior surface is brought 
about, we can, I think, most easily conceive the influence to be due 
to some kind of tension or pull of the new material which is of such a 
sort that it restrains the development of a head at a more posterior 

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INTERNAL FACTORS OF REGENERATION IN ANIMALS 



65 



level. We can picture to ourselves the same kind of process taking 
place in the regeneration of the tail of a fish from an oblique surface. 
The maximum rate of growth is found over that part of the cut-sur- 






FlG. 31. — Plannria lugubris, A. Showing how worm was operated upon. B. A single head 
regenerated at anterior cross-cut. It was united by a line of new tissue along the side of 
the long half-piece with the new tissue at the anterior end of the short half-piece. The two 
half-pieces reunited along the middle line. C. Two heads regenerated, one from each half 
cross-cut The two half-pieces were kept apart along the middle line. 

face that is nearer the base of the tail (Fig. 40). At all other points 
the growth is retarded, or held in check, and it can be shown that 
the suppression is connected with the formation of the typical form 
of the tail in the new part. If we cannot actually demonstrate at 
present that this is due to some sort of tension between the different 
parts which regulates the growth, we find, nevertheless, that it is by 
means of some such idea as this that we can form a clearer concep- 
tion of how such a relation of the parts to each other is established. 
In a later chapter this subject will be dealt with more fully. 



THE INFLUENCE OF THE NUCLEUS ON REGENERATION 

The influence of the nucleus on the process of regeneration has 
been shown in a number of unicellular forms. It was first observed 
by Brandt in 1877 that pieces of Actiftosp/icerintn eichhomii that con- 
tain a nucleus assume the characteristic form, but pieces without a 
nucleus fail to do so. Schmitz ('79) found that when the wall 
of the many-celled siphonocladus is broken, the protoplasm rounds 
up into balls, some of which contain one or more nuclei, while 

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GS REGENERATION 

others may be without nuclei. The nucleated pieces produce a new 
membrane, and later become typical organisms, but non-nucleated 
pieces do not form a new membrane, and soon disintegrate. Nuss- 
baum ('84, *86) cut into pieces the ciliate infusoria, oxytricha and 
gastrostyla. Those pieces that contained a nucleus quickly regener- 
ated a new whole organism of smaller size, that had the power of 
further reproduction, while the pieces that did not contain a part 
of the nucleus showed no evidence of regeneration ; and, although 
they continued to move about for as much as two days, they subse- 
quently disintegrated. Gruber obtained the same result on another 
ciliate infusorian, Stentor coeruleus. He found that, although the 
non-nucleated pieces close over the cut-surface, and move about for 
some time, they eventually die. He further showed that a non- 
nucleated piece containing a portion of a new peristome in process 
of formation will continue to develop this new peristome, although a 
new peristome is never produced by a non-nucleated piece under 
other circumstances. He believes that if the new peristome has 
begun to be formed under the influence of the old nucleus, it may 
continue its development after the piece is severed from its connection 
with the nucleus. A non-nucleated piece containing a part of the 
old peristome does not produce a new peristome from the old piece. 
Gruber observed that a non-nucleated piece of amoeba behaves differ- 
ently from a nucleated piece, and dies after a time. 

Klebs found that when certain algae are put into a solution that 
does not seriously injure them, but causes the protoplasm to contract 
into balls, some of these contain nuclei, others not. If, for instance, 
threads of zygnema, or of spirogyra, are placed in a 16 per cent solu- 
tion of sugar, the protoplasm of each cell breaks up into one or more 
clumps, some with nuclei, others without. Both kinds may remain 
alive for a time; some of the non-nucleated pieces may live for 
even six weeks. The nucleated pieces surround themselves at once, 
when returned to water, with a new cellulose wall, but the ndn-nucle- 
ated pieces remain naked. The latter can, nevertheless, produce in 
the sunlight new starch that is used up in the dark and is ma'de anew 
on the return to Hght.^ 

Balbiani (*88) found that non-nucleated pieces of cytrostomum, 
trachelus, and protodon failed to regenerate, and Verworn ('89 and 
*92) obtained similar results on several other protozoa. Similar 
facts have been made out by Hofer ('89), Haberlandt and Gerassi- 
moff ('90). Palla (*9o) found that in certain cases non-nucleated 
pieces, especially those from cells in growing regions, can produce a 
new cell wall; while more recently Townsend (*97) has shown in 

^ In other plants, fumaria, for example, non-nucleated pieces do not seem to be able to 
make new starch after using up that which they contain at first. 



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INTERNAL FACTORS OF REGENERATION IN ANIMALS 6/ 

several forms that non-nucleated pieces do not produce a new cell 
wall unless they are connected by protoplasmic threads with nu- 
cleated pieces. The most delicate connection suffices to enable a 
non-nucleated piece to make a cell wall, even when the nucleated 
piece lies in one cell and the non-nucleated in another, the two being 
connected by a thread of protoplasm that passes through the inter- 
vening wall. 

If we examine somewhat more in detail some of these cases, we 
find that when a form like stylonychia is cut into three pieces, the two 
end-pieces without a nucleus fail to regenerate, while the central 
piece makes a new entire organism of smaller size. If stentor is cut 
into three pieces, each piece containing one or more nodes of the 
macronucleus, each produces a new stentor. If, however, a piece is 
cut off so that it does not contain a part of the macronucleus, it 
fails to regenerate. Verwom ('95) succeeded in removing the central 
capsule with its contained nucleus from the large radiolarian, Ttiallasi- 
colla nucleata. The non-nucleated animal remained alive for some 
time, but eventually died. The nucleated capsule developed a new 
outer zone with processes like those in the normal animal. If the 
nucleus is taken from the capsule, the capsule dies, but shows some 
traces of the formation of an outer zone. If the protoplasm is re- 
moved as far as possible from around the nucleus, the latter does not 
regenerate new protoplasm, but dies after a time. Verworn con- 
cludes that the protoplasm cannot carry on all its normal functions 
without the nucleus, or the nucleus without the protoplasm. 

These experiments sufficiently demonstrate that non-nucleated 
pieces are unable to regenerate. If we attempt to examine further 
into the meaning of the phenomenon, we find a few things that 
appear to have a bearing on the result. The behavior of the non- 
nucleated pieces shows that the metabolism of the cell has been 
changed after the removal of the nucleus. In some cases the 
protoplasm is not able to carry out the process of digestion of the 
included food substances. This process may be due to some inter- 
change that goes on between the nucleus and the protoplasm, 
which is stopped by the removal of the nucleus, and, in consequence, 
the metabolism of the cell is changed. The lack of regenerative 
power may be due to this change in the metabolism. It cannot be 
claimed, however, that the result is due to a lack of energy in the 
pieces, for the incessant motion of the cilia in some kinds of pieces, 
that goes on for several days, shows that a large store of energy is 
present. Unfortunately, we do not know enough of the relation that 
subsists between the nucleus and the protoplasm to be able to state to 
what the lack of regenerative power is due. 

Loeb ('99) has suggested that the lack of power of non-nm;leated 

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68 REGENERATION 

pieces may be due to a lack of oxidation. The nucleus contains 
substances which, according to Spitzer, are favorable to the process 
of oxidation. When the nucleus is removed, the oxidation is sup- 
posed by Loeb to be too low to allow the process of regeneration to 
take place. In support of this view, he points out that while non- 
nucleated pieces of infusoria live for only two or three days, non- 
nucleated pieces of plants containing chlorophyl may be kept alive 
for five or six weeks. Non-nucleated pieces containing chlorophyl 
can obtain a supply of oxygen, owing to the breaking down of carbon 
dioxide in the chlorophyl-bodies, and the consequent setting free of 
oxygen. It should be pointed out, on the other hand, as opposed to 
Loeb's view, that non-nucleated pieces of amoeba have been kept 
alive for fourteen days ; and that despite the better oxidation that 
may take place in non-nucleated pieces of plants, regeneration does 
not take place. 

It has been found that non-nucleated pieces of the egg of the 
sea-urchin do not segment or develop, and the result is the same 
whether the pieces come from fertilized or unfertilized eggs. If, 
however, a spermatozoon enters one of these pieces, the piece will 
segment, and, as Boveri and later Wilson have shown, it will produce 
an embryo. 

Boveri also tried fertilizing a non-nucleated piece of the egg of 
one species of sea-urchin with a spermatozoon of another species. 
He found that the embryo that develops is of the type of the species 
from which the spermatozoon has come, and he concluded that the 
nucleus determines the character of the larva, and that the protoplasm 
has no influence on the form. The evidence from which Boveri 
drew his conclusion is not beyond question. It has been shown by 
Seeliger ('95) and myself ('95) that if whole eggs of the species 
Spharechinns graniilaris, used by Boveri, are fertilized by the sper- 
matozoa of the other species. Echinus microtuberculaUis^ there is 
great variability in the form of the resulting larvae. Most of them are 
intermediate in character between the types of larvae of the two 
species, but a few of them are like the paternal type. Vernon ('99) 
has more recently shown that the character of hybrids is dependent 
upon the ripeness of the sexual products of the two parents. If, 
for instance, the eggs (sphaerechinus) are at the minimum of maturity, 
the hybrids are more like the male (strongylocentrotus). 

It remains, therefore, still to be shown whether or not the proto- 
plasm has any influence on the form of larva that comes from a non- 
nucleated piece, fertilized by a spermatozoon of another species. 
That the nucleus of the male does have an influence on the form of 
the animal is abundantly shown by the inheritance of the peculiarities 
of the father through the chromatin of the spermatozoon. 

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INTERNAL FACTORS OF REGENERATION IN ANIMALS 69 

THE CLOSING IN OF CUT-EDGES 

One of the most familiar changes that takes place when a cut-edge 
is exposed involves the rapid covering over of the exposed tissues. 
This takes place from the margin of the wound, and a layer of cells, 
usually the ectoderm at first, covers the surface. The closing in is 
brought about in many forms by the contraction of the muscles of 
the outer wall of the body. This seems to be the case in the earth- 
worm and in the planarian, as well as in other animals, such for in- 
stance as the starfish, holothurian, etc. But in addition to this 
purely muscular contraction another process takes place, that is less 
conspicuous in forms in which the muscles bring about the first clos- 
ing, but which is evident in forms in which the muscles are absent 
or little developed. I am able to cite two striking cases that have 
come under my own observation. When a piece is cut from the stem 
of tubularia, the ends close in twenty minutes to half an hour. The 
body wall, the coenosarc, composed of the two layers of ectoderm and 
endoderm, withdraws a little from the cut-edge of the outer hard tube, 
or perisarc, that covers the stem, and then begins to draw across the 
open end. A perfectly smooth, clean edge is formed that advances 
from all points to the centre, where the final closing takes place. The 
closing is not due to an arching over of the coenosarc, but the thin 
plate is formed standing nearly at right angles to the outer tube. 
This plate is composed of two layers of cells, of which there are a 
number of rows arranged concentrically between the centre and the 
outer edge. In the absence of muscle-fibres in the stem, the result 
cannot be due to a muscular contraction, and even if short fibres 
existed the transportation of cells entirely across the open end would 
speak against this interpretation.^ Since the closing over takes place 
without any support, we cannot suppose the process to be due to 
any sort of cytotropic effect. The closing takes place equally well 
in diluted sea water and in stronger solutions. The method of 
withdrawal of the cells, as best seen when longitudinal pieces are 
studied, resembles very much the withdrawal or contraction of proto- 
plasmic processes in the protozoa, and so far as one can judge from 
resemblances of this sort, the two processes appear to be the same. 

This closing in of the cut-surface, while a preliminary step in the 
process of regeneration, cannot, I think, be regarded as a part of the 
regeneration in a strict sense. That the two processes are not 
dependent on the same internal factors is shown by the following 
experiments : If a bunch of tubularia is kept in an aquarium, it will 

* I have found that the closing in takes place equally well when one per cent of KG is 
added to the sea water. This salt has, as Loeb has shown, an inhibiting effect on muscular 
contractility, — not, however, on amoeboid movements. ^ I 

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70 REGENERATION 

produce new heads two or three times and then cease, and if after the 
last-formed heads have died, pieces of the stem are cut off, they close 
as readily as do pieces from fresh hydroids. Moreover, at certain 
times of year the species Tubularia {Parypha) crocea lose their 
heads, and only the stalks remain. Pieces of these stalks will not 
regenerate new heads, at this time, although they close in as quickly 
as do pieces at other times of the year when the heads are present 
and when new ones regenerate. 

Another equally good illustration of what seems to be the same 
phenomenon is found in the closing in of wounded surfaces in the 
young tadpole embryos. If embryos are taken from the jelly mem- 
branes, or even after they have been set free, and cut in half, each 
piece quickly covers over the wounded surface by means of the ecto- 
dermal cells. A much more striking illustration of this closing over 
in the young tadpole is obtained by cutting, with a pair of small scis- 
sors, a large piece from the side. The area may be a fourth or more 
of the entire side, and yet it may be closed over in an amazingly short 
time. Half an hour or an hour often suffices to cover a large exposed 
surface. In this case also the wound is covered not by individual 
cells wandering over the exposed surface, but by a steady advance of 
the smooth edge of the ectoderm toward a central point. The process 
is so similar to that which takes place in tubularia that little doubt 
can remain as to the two being due to the same factors. As there are 
no muscle fibres present in the part of the frog's embryo from which 
the piece is cut off, the result cannot be due to muscular contraction, 
but appears to be a contractile phenomenon similar to that in tubularia. 
Even the small piece that is cut from the side of the body shows the 
same phenomenon. At first it suddenly bends outwards owing to some 
physical difference between the inner and the outer parts of the 
piece. Then the edges thicken, bend in, and begin their advance over 
the inner tissues. The process is seldom completed, since there 
appears to be a limit to which the ectoderm can be stretched as the 
edges advance. A most striking phenomenon both in pieces of tubu- 
laria and of the frog's embryo is the entire absence of dead material 
at tlie wounded surface. No sooner is the operation performed than 
the advance begins, and there is not a trace of dying cells or parts of 
cells to be seen. 



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CHAPTER IV 

REGENERATION IN PLANTS 

The series of experiments that Vochting has carried out on the 
regeneration of the higher plants are so much more complete than all 
previous experiments, and his analysis of the problems concerning 
the factors that influence regeneration is so much more exact than 
any other attempts in this direction, that we may profitably confine 
our attention largely to his results. Many of his experiments were 
made with young twigs or shoots of the willow (salix), which, after 
the removal of the leaves, were suspended in a glass jar containing 
air saturated with water. Under these circumstances the pieces pro- 
duced new shoots from the buds (leaf-buds) that are present near the 
point at which the leaves were attached, and new roots, in part from 
root-buds, that are also present on the stem. 

If the piece is suspended in a vertical position with its apex 
upward (Fig. 32, A\ small swellings appear after three or four days 
near the lower, i.e, the basal, end of the piece. These break through 
quickly and grow out as roots. If a leaf-bud is present near the 
basal end of the piece, the first roots appear at the side of or under 
this; later others appear around the same region. The first roots 
to appear under these conditions come from pre-formed root rudi- 
ments, the others are, in part at least, new, adventitious roots. If 
the lower end of the cut is made through the lower part of a long 
internofle, i.e, just above a bud, the roots appear as a rule only near 
the cut-end, and few if any of the roots develop at the first bud above 
this region. In many cases there is formed over the basal cut-surf gee, 
in the region of the cambium, a thickening, or callus, and not infre- 
quently from this also one or more roots may develop. The direction 
taken by the new roots is variable, being sometimes downward, 
sometimes more or less nearly at right angles to the stem. 

While these changes have been taking place at the base, the leaf- 
buds at the apical end have begun to develop. One, two, three, four, 
or even five of the higher buds begin to elongate, the number and 
extent of development depending on the length of the piece. The 
topmost or apical bud grows fastest, and the others grow in the order 
of their position. In the region below the lowest bud that/iievelop6 

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72 



REGENERA TION 



there may be one or more buds that do not grow ; but if the piece is 
cut in two just above these buds, they will then grow out. 

The results show that at the base of the piece the same factors 
that bring about the development of the rudiments of preexisting 
roots also cause the development of new roots, if the lower end is 
in a region in which there are no rudiments of roots present. The 






Fig. 32. — After VOchting. A, Piece of willow cut off in July, suspended in moist atmosphere with 
apex upward. B. Older piece of willow (cut off in March) suspended in moist atmosphere 
with apex downward. C Piece of willow with a ring removed from middle. Apex upva'ard. 

D, Piece of root of Populus dilatata. Basal end upward. Shoots from basal callas. 

E. Piece of root of same with two rings removed. New shoots develop from basal callus, 
and from basal end of each ring. 

influence that produces the new roots is confined to the basal part 
of the piece. In the apical part of the piece there are no adventi- 
tious structures produced, but a longer region is active, and several 
pre-formed leaf-buds begin to elongate. The topmost shoot grows 
faster than the others, showing that the influence that produces the 
growth is stronger near the apical end than at points further removed. 
If another piece of a willow stem be placed under the same condi- 

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REGENERATION IN PLANTS 73 

tionSy but suspended with the basal end uppermost, results that are 
in many respects similar to the last are obtained. Roots appear 
around the base of the piece, i,e, around the upper end, and the leaf- 
buds that develop are those that stand nearest to the apical, at present 
the lower, end of the piece. 

These results seem to indicate that, in the main, the chief factors 
that determine the growth of the new part are internal ones; and 
although internal factors do appear to be the dominating ones, since 
roots appear in both cases at the base and shoots at the apex, yet it 
would be wrong to conclude that gravity has no influence at all on the 
result. In fact, other experiments show that it does have an influence. 
If an older branch (8-12 mm. in diameter) is cut off and hung up 
with its base upward^ the result is somewhat different from that with 
younger branches. The roots appear along the entire length of the 
piece, as shown in Fig. 32, B\ the largest are those near the base, 
and they decrease in size toward the apex of the piece. It is also 
noticeable that all the roots come from preexisting root-buds, and no 
adventitious roots are formed, even at the base. The leaf-buds that 
develop are those arising near the apex, as in the last experiments. 
They bend upward as they grow longer. A comparison of the 
results obtained from younger and older pieces may, at first, seem 
to show that the difference in their development is due to the greater 
amount of reserve food stuff in the older piece, and Vochting thinks 
it probable that this influence may account for the strength, length, 
and even for the number of roots that develop, but he believes that it 
is improbable that their mode of origin and their location can be so 
determined. Furthermore, the development of new roots around 
the base of the younger piece can hardly be explained as due to the 
absence of food stuff. The explanation of the production of a smaller 
number of roots in a young piece is that its tissues are less highly 
specialized, its buds less advanced, and the piece itself is in a lower 
stage of development. Another explanation must be found for the 
greater number of roots that develop in the older piece. This is due, 
as Vochting tries to show, in part to the influence of gravity on the 
piece. 

Vochting's general conclusion is that "the force or forces that 
determine Xh^ polar differences in the piece are most evident and most 
energetic in very young twigs ; that this difference decreases with the 
age of the twig whose leaf-buds and root-buds become further devel- 
oped. It is clear that the new roots of young twigs could appear in 
corresponding number and strength in exactly the same regions in 
which they grow out from pre-f ormed buds of a year-old tivig. Since 
this does not occur, and since the roots appear only near the base of 
young twigs, the explanation must be that the innate polar forces 

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74 



REGENERATION 



act more energetically in young twigs, and the buds that develop 
in the older twigs must arise in antagonism to the action of this 
force." The polar difference between apex and base is present, 
nevertheless, as Vochting's experiments show, even in quite old 
pieces. 

A series of experiments was carried out with the intemodes of several 
plants in order to see if, in the absence of pre-formed buds, new buds 




Fig. 33. — After Vftchting. A. Intemodal piece of Begonia discolor. Apex upward. B, Same 
with apex downward. C, Intemodal piece of Heterocentron diverstfolium. Apex upward. 
A E. Pieces of leaf of Heterocentron diversifolium. Apex downward. F. Same with apex 
upward. D, E, F. Same planted in earth. 

would develop. The experiments were undertaken in order to ascertain 
whether the same polarity, exhibited by longer pieces, would be also 
found in intemodal pieces. In most plants pieces of this kind do not 
produce new structures, but in Heterocentron diversifolium an internode 
produces roots at its basal end without regard to the position of the 
piece (Fig. 33, C), Leaves do not appear on these pieces. On the 
othef hand internodes of Begonia discolor give the opposite result, as 

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REGENERATION IN PLANTS 75 

shown in Fig. 33, A, B, In this case leaf-buds appear at the apex of 
the internodal piece (Fig. 33, A\ even when the apical end is down- 
ward (Fig. 33, B), From the bases of the new shoots roots may then 
develop, as also shown in the figure (Fig. 33, B). Vochting con- 
cludes that the same polarity that is a characteristic feature of longer 
pieces is also present in internodal pieces. 

It is not necessary to separate completely portions of the stem in 
order to produce roots near one end and shoots near the other. If a 
ring, including the cambium layer, is cut from the piece, as indicated 
in Fig. 32, Cy the part above and the .part below act independently of 
each other, and each behaves as a separate piece. In various other 
ways the same result may be obtained, as by simply making an 
incision in the stem at one side, or by partially splitting off parts of 
the stem (Fig. 34, C). 

If instead of a piece of the stem, a piece of a root is removed, 
the results are as follows. ^ It should be remembered that the 
basal end of a root is the part nearer the stem, the apex is 
the part nearer the apex of the root. If pieces of the root of the 
poplar, Populus dilatata, are suspended vertically (Fig. 32, D) in a 
moist chamber, a covering of new cells, a callus, appears over the cut- 
ends. From the basal callus numerous leaf-shoots may develop. 
Pieces of large roots may produce over a hundred of these shoots 
from a single basal callus. In some cases adventitious shoots 
may also arise from the side of the root near the basal end. 
Roots develop from the callus over the apical end ; less often from 
the sides near the end. If a similar piece of root is suspended with 
its apical end upward, the new shoots arise as before over the basal 
end, that is now turned downwards. 

The leaves of some plants, as has long been known, are able to 
produce new plants. • The begonias are especially well suited for ex- 
periments of this kind. A piece of the stalk of a leaf suspended in a 
moist atmosphere produces roots near its base. In most cases the 
opposite end of the stalk, ix, the end nearest the leaf, putrefies and 
slowly dies toward the base. Near the base there may arise, before 
the breaking down of the piece has reached this point, leaf-buds that 
arise just above the first-formed roots. When these new shoots ba/e 
reached a certain size they may produce their own roots at or near 
the base. If, however, a portion of the leaf is left attached to the 
leaf-stalk (Fig. 35, A\ new roots arise near the basal end of the stalk, 
and later shoots grow out near the point of union of the leaf and its 
stalk at the point where the veins of the leaf come off. These shoots 
produce roots of their own near the base, and roots may also appear 
on the part of the leaf-stalk near its union with the lamma. If a 

1 Knight obtained similar results in 1809. 

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76 REGENERATION 

part of the mid-vein, or of any large vein of the leaf, is cut out, leav- 
ing a part of the lamina on each side (Fig. 35, B\ and the piece is 
suspended vertically, roots appear on the basal end of the vein, and 
in the same region one or more shoots arise. 

Leaves of heterocentron with the stalk attached, if kept in diffuse 
light, produce roots along the stalk, especially near the basal end, 
but shoots do not appear, even after five months (Fig. 35, C), 

These experiments show that the leaves do not exhibit the same 
polar relations that are shown by pieces of the stem and root. 
Vochting points out that the rjesults may be explained in either of 
two ways. The stem and the root have in general an unlimited 
growth with a vegetative point at the apex. The leaf has only a 
limited growth. Its cells form permanent tissue, hence the leaf does 
not produce a new plant from its outer part. The second possibility 
is this : the phenomenon is connected with the symmetrical relations 
that different structures possess. Stem and root are symmetrical in 
two or more directions, the leaf on the other hand is a flat structure 
with one plane of symmetry, and even symmetry in one plane may 
be absent. If the leaf could produce shoots at its apex and roots at 
its base, from the semilunar fibrovascular bundle of the leaf, then an 
individual (the leaf) with its single plane of symmetry would produce 
shoots and roots that are symmetrical in two planes. Such a result 
would be so anomalous that one may well doubt the possibility of its 
coming into existence.^ 

Later, Vochting attempted to see if the same relation found in the 
leaf would hold for other organs that have a limited growth. He 
found that such structures, as spines, for example, produce both 
shoots and roots near the base, as do leaves. 

These experiments of Vochting on the regeneration of pieces of 
the higher plants show that a piece possesses an innate polarity, or 
" force," as Vochting sometimes calls it (although he explicitly states 
that he does not use the word " force " in its strict, physical sense). 
It does not follow, of course, that external conditions may not also 
influence the regeneration, but in those experiments in which the 
pieces were freely suspended in a moist atmosphere, the external fac- 
tors are as far as possible excluded, so that the effect of the innate 
tendencies are most clearly seen. In another series of experiments the 
influence of external conditions on the regeneration was especially 

1 Vochting points out that a parallel case is found in certain conifers. In these there 
arise from a vertical many-sided main stem whorls of side branches that are symmetrical in 
one plane. These lateral branchtfs, if cut off and planted, produce new roots and new 
branches, but the latter are always side-branches, like the parts from which they arise. They 
never produce a normal main axis. Nevertheless, although these branches cannot them- 
selves produce a main shoot, a callus may be formed at the base of the piece, and from 
this a new main stem may arise. 

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REGENERATION IN PLANTS TJ 

Studied. This analysis that Vochting has made of the problem of 
regeneration is in the highest degree instructive, since it shows how 
several factors, — some internal, others external, — take a hand in the 
result ; and it is only possible to unravel the problem by combining 
different experiments carried out in such a manner that one by one 
the different factors at work are separated. 

If a piece of a young stem of Salix vintinalis is suspended ver- 
tically in a moist atmosphere, with the lower end in water (for | of a 
centimetre), and the piece kept in the dark, the result is, in the main, 
the same as when similar pieces are suspended in moist air without 
coming into contact with water. Roots arise near the base, and 
shoots near the apex, without regard to which end is in the water. 

If the same experiment is repeated in ordinary air, i,e, air not 
saturated with water, the result is somewhat different. If the twig 
is suspended vertically with its apex upzvard, roots soon appear on 
the basal end that is in the water, but no roots develop above the 
water. Small protuberances may appear above the water in the 
places at which roots would develop if the piece were surrounded by 
a moist atmosphere, but they do not break through the bark. If the 
piece is then covered by a jar containing air saturated with moisture, 
these protuberances may become roots. It is clear, therefore, that 
the dryness of the air has prevented their development. 

If a similar twig is suspended (in the air) with its apex downward^ 
and the lower end in water, root protuberances appear, at first, only 
around the base, i.e. at the upper end. Under the water, at the 
apical end, small and weak roots may develop, or may even not 
appear at all. 

These results agree, in the main, with those in which the piece is 
surrounded by moist air, and give evidence of an inner polarity that 
is an important factor in the regeneration. The results show that in 
a piece with the basal end in water and the rest of the piece in the 
air the tendency to produce roots above the water is suppressed by 
the dryness of the air. In an inverted piece, however, with the apex 
in water, the innate tendency to produce roots at the basal end is 
strong enough to overcome the effect of the dryness of the air to 
suppress their development. The abundance of water absorbed 
by the apex of the piece makes the development of the roots possible 
under these conditions despite the dryness of the air.^ 

There is another factor connected with the submergence of the 
end of the stem in water that can be shown by putting a longer part 
of the end under the water. Neither roots, if it is a basal end, nor 
leaf-buds, if it is an apical end, appear on the deeper parts of the 
submerged end. This is due, in all probability, to the insufficiency 

* A piece suspended in ordinary air dries up without producing any new sti^ictures. ^ 

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78 REGENERATION 

of oxygen in the water, and as a result the buds are prevented from 
developing. 

It can be shown that light has also an influence on the regen- 
eration of pieces, and that it has a stronger influence on some plants 
than on others. In some plants roots develop only on that side of 
the stem that is less illuminated. In Lepismium radicans, for in- 
stance, adventitious roots are produced by the plant even in dry air. 
Pieces of the stem can produce roots on either the upper or the 
lower surface, according to which side is less illuminated. A 
piece of the stem of this plant that had been kept in the dark pro- 
duced two roots, one above and one below, — one, therefore,. opposed 
to the direction of the action of gravity, and the other in the direction 
of that action. Even in pieces of the willow, suspended in a moist 
atmosphere, roots develop better and over a greater length of the 
stem on the less illuminated side. 

Although the experiments with pieces of young willow-twigs may 
seem to show that gravity is not a factor in regulating the develop- 
ment of the new parts, the results show in reality only that internal 
factors have a preponderating influence. By means of another series 
of experiments it can be shown that gravity does have an influence on 
the production of the new parts. It is evident that in order to test 
the action of gravity, pieces must be placed in different positions in 
relation to the vertical. It will be found, if this is done, that different 
results are obtained according to the angle that the piece makes with 
the vertical. If a piece is suspended in a moist atmosphere, with its 
apical end upward, the smaller the angle that the piece makes with 
the vertical so much the more are the leaf-buds that develop confined 
to the upper part of the piece, and so much the more do they develop 
from all sides of the upper end ; conversely, the greater the angle 
with the vertical, i.e. the more nearly horizontal the position of the 
piece, so much the more are the leaf-buds that develop found along 
the upper side of the apical end (as well as around the end). If the 
piece is placed in a horizontal position, the leaf-buds develop not only 
around the apex, but they develop along the entire length of the upper 
surface, best, however, near the apical end. 

If similar pieces are suspended in oblique positions, with the basal 
end upward, different results are obtained. In the preceding experi- 
ment the polarity of the piece and gravity act together, while in this 
experiment their action is opposed. Although there is a great 
amount of variability in the results, yet the action of gravity is found 
to have less influence on the result than has the inner polarity, and 
the influence of the latter is so much greater that the action of gravity 
is hardly noticeable. 

The roots do not show as markedly the influence of gravity as 

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REGENERATION IN PLANTS 



79 



do the leaf-buds, yet Vochting has found that the position in which 
they appear varies with the position of the piece with respect to the 
vertical. 

In the preceding cases the rudiments of the leaf-buds and of the 
roots were probably present in most cases, so that gravity only 
awakens them into activity. In other forms, as, for instance, in 





FIG. 



-U. — After VOchtkig. A. End of a piece of Heterocentron diver sifolium. 
B. Piece of same bent and suspended " with concave-side upward." " 



Apex downward. 
C, Piece of a stem of 
Salix viminalis. Apex upward. A piece of the side has been lifted up and two wedges 
inserted. 



heterocentron, it is possible to show that gravity may even determine 
the production of new buds. If pieces of the end of a branch, 
including the growing point, are suspended vertically, some with the 
apical end upward, others with the basal end upward (Fig. 34, A\ 
the former produce roots only around the base, but in the latter 
roots appear frequently, not only at the base, but even extending 
along the stem. They appear not only at the nodes, where pre- 

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8o REGENERATION 

formed rudiments may be present, but also in the internodes, where 
there are no rudiments of roots. 

Stems of heterocentron placed in a horizontal position produce a 
circle of roots around the base, and later, in several cases, roots from 
the under surface of the stem, both from the nodes and the inter- 
nodes; but these roots are smaller than those at the base. Those 
. around the base are often longer on the lower side than on the 
upper side. 

Vochting has also studied the regeneration of pieces of roots of 
the poplar and of the elm suspended horizontally in a moist chamber. 
A callus develops from the cambium region of the basal end, and 
from this a thick bunch of adventitious sprouts grows out. A weak 
callus may develop on the apical end also, from which a few roots 
develop. In other cases adventitious shoots are produced also from 
the apical callus, especially from the upper edge of the callus. 
The, results are variable, but show that at times leaf -shoots may 
develop from the apical end of the root. It is also singular to find 
that, while pieces of the root produce new leaf-shoots very readily, 
yet they often fail to produce new roots, or produce only a few that 
arise from the apical callus or from the sides near that region. It is 
difficult to show that gravity has any influence on the result. 

Vochting recognizes another sort of influence that determines the 
position of new organs on a piece. If a young, growing end of a 
stem of Heterocentron divcrsifolium is suspended by two threads in 
a horizontal position, the ends bend upward as a result of the nega- 
tive geotropism of the piece. The new roots appear at the base of 
the piece, and also on the convex side of the bent part of the stem, as 
shown in Fig. 34, B. The same result can be obtained by forcibly 
bending a twig, and then tying the ends together, so that it remains 
in its bent position. If a piece of this sort is suspended in a moist 
atmosphere, with the bent inner concave side turned upward, the 
roots appear on the base and at the bend, especially on the under 
side, both from the nodes and internodes. If now in order to see if 
gravity takes any part in the result the next piece is suspended with 
the outer coTtvex side of the bent part turned upward, it is found that 
many of the pieces produce roots only at the base, but others pro- 
duce roots also at the bent portion of the stem, but they are fewer 
than in the last experiment. The roots arise for the most part on the 
under side of the arch, and only a few arise from the upper part. It 
is clear that gravity is also one of the factors in the result. Leaf- 
buds arise in these pieces with the concave side turned upward ovAy 
near the apex ; rarely one may develop on the lower part of the basal 
end. In pieces with the concave side turned downward the leaf-buds 
arise for the most part at the apex, but sometimes they appear on the 

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REGENERATION IN PLANTS 8 1 

upper part of the basal arm. The results are due to two factors, 
gravity and an inner "force'' that is supposed to be the resultant of 
a growth phenomenon taking place in the bent portion. Vochting 
supposes that a process of growth takes place as a result of the bend- 
ing; "the plasma streams to this region, and a new development 
takes place here more easily." Vochting adds that this view will not 
explain the morphological character of the new organs, and that this 
must be due to quite other causes. The results may, I venture to 
suggest, find a simpler explanation as the result of the bending, dis- 
turbing the tensions of the protoplasm, causing the two arms of the 
piece to act as if they had been separated from each other. This 
idea is more fully developed in a later chapter. 

Sachs has criticised Vochting's general conclusion in regard to the 
internal factors that determine the regeneration in a piece of the stem 
of a plant. He gives very little weight to the innate polarity of the 
piece, and attempts to explain the results as due to certain substances 
in the stem of such a sort that, accumulating in any region, they 
determine the kind of regeneration that takes place. Sachs also as- 
sumes that gravity acts on these substances in such a way that 
the root-forming substances flow downward and the shoot-forming 
substances flow upward. In a piece of a stem, the two formative sub- 
stances contained in it accumulate at the two ends, and determine 
the kind of regeneration that takes place. It is evident that Sachs' 
hypothesis fails to explain the method of regeneration of an inverted 
piece suspended in a vertical position, since the roots appear at the 
upper end and the shoots at the lower end. Sachs explains this as 
the result of the previous action of gravity on the piece, while the piece 
was a part of the tree and stood in a vertical direction. He supposes 
the longer time that gravity has acted on the piece has determined its 
basi-apical directions, so that this influence is shown in the inverted 
piece, rather than the action of gravity on it in its new position. 
This conception involves quite a different idea from the original one 
of formative substances flowing in definite directions. Moreover, 
Vochting has met this interpretation by using the twigs of the weep- 
ing willow, that hang downward on the tree. If gravity has acted on 
these drooping twigs in the way that Sachs supposes it can act, then 
we should expect to find, if Sachs' view is correct, that roots would 
develop at the apical end of a piece of the twig, and leaves at the 
• basal end, if the piece is hung vertically with its basal end {i.e. the 
end originally nearer the trunk of the tree) upward. The regeneration 
of these pieces shows, however, that they behave in the same way as do 
pieces of twigs that have always stood vertically on the tree. There 
can be, therefore, no doubt that the distinction between base and apex 
is an expression of some innate quality of the plant itself. That an 

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82 REGENERATION 

external factor, gravity, is also a factor in the regeneration of the 
pieces, is abundantly shown by the experiments of Vochting and 
others, but that innate factors are also at work cannot be doubted. 
We find evidence in many animals of a similar difference between the 
two ends of a piece, and we speak of this difference between the ante- 
rior and posterior ends of a piece as its polarity. What this polarity 
may be we do not know, and it is even doubtful whether we should be 
justified in speaking of it as a force in the sense that the difference in 
the ends of a magnet is the result of a magnetic force. The kind 
of polarity shown by animals and plants does not seem to correspond 
to any of the so-called forces with which the physicist has to deal, but 
a further discussion of this question will be deferred to a later chapter. 

The preceding account of regeneration in some of the higher 
plants has shown that their usual method of regeneration is by means 
of latent buds that are present along the sides of the stem, or by 
means of adventitious buds that develop anew along the sides of 
the stem. In a few cases new buds may develop from the new tissue 
of the callus that forms over the cut-ends, but in such cases the new 
shoots, or the new roots, are much smaller in diameter than the end 
from which they arise, and usually several or many new shoots de- 
velop on the same callus. In these respects the regeneration of the 
higher plants is different from that of the higher animals, ♦for, in the 
latter, the new part arises from the entire cut-surface. This differ- 
ence is no doubt connected with differences in the normal method 
of growth in plants and in animals, and an explanation of the growth 
would, perhaps, also give an explanation of the mode of regeneration. 
The normal method of growth in higher plants takes place largely by 
the formation of lateral buds, as well as by terminal growth, and we 
find that regeneration takes place in most cases from the same lateral 
buds or from others of a similar kind that develop after the piece has 
been separated. 

It is sometimes stated that the higher plants do not regenerate at 
the cut-ends, because they produce buds at the sides. The statement 
implies that there is some sort of antagonism between the regenera- 
tion of a bud at the end, and the development of buds at the side. It 
may be true that the development of a latent bud at the side might 
suppress the tendency to produce a bud at the end, if such a tendency 
exists ; but if we remove the lateral, pre-formed buds, new ones 
develop at the sides, and not at the end. That there need not be an 
antagonism between the formation of a bud, or of buds, at the end, 
and also at the sides, is shown in Vochting's experiments with the 
roots of the poplar. In these, leaf-shoots and root-shoots developed 
both from the callus over the cut-end, and at the side of the piece also. 
It has further been shown that, although a piece of the internode does 

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REGENERATION IN PLANTS 



83 



not produce new leaf-buds at the sides, neither does it regenerate a 
new apical bud at the end. 

A most interesting fact connected with the regeneration of the 
higher plants is, as has been pointed out, that even when a callus is 
formed over the cut-end, and new growth takes place from this callus, 






D 



F^G. 35. — After VSchting. A. Leaf-stalk of Begonia rex with a portion of the lamina. Sus- 
pended with base upward. B. Piece of lamina of leaf of same. C. Leaf of Heterocentron 
diversifolium, D, Leaf-stalk of Begonia discolor. 

there is produced, not a single terminal bud, but a number of separate 
buds. The piece does not complete itself, but produces new buds, 
that make new branches. The explanation of this mode of regenera- 
tion in plants is not known. It appears to be connected with the 
production, by means of buds, of all the new structures. Why this 
should occur we do not know, and the only suggestion that offers 

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84 REGENERATION^ 

itself is that the result may be in some way connected with the hard 
cell walls in plants that make difficult the organization of large areas 
into a new whole. As a result, the new development takes place in a 
small group of similar cells, that are sufficiently near together to 
organize themselves into a whole despite the interference met with in 
the cell walls. 

Vochting has also studied the regeneration of pieces of the liver- 
wort, Lunularia vulgaris. The results have been already partly given 
in the first chapter. If cross-pieces are taken from the thallus, each 
produces a new bud at its anterior or apical end (Fig. 9, A^ A ^). The 
new bud arises from the cut-surface, or very near it, from a group of 
cells of the midrib that lies nearer the under side (Fig. 9, A'^), The 
bud gives rise to a new thallus that springs from a narrow base at its 
origin from the old piece. If a piece is cut longitudinally from the 
thallus along the old midrib, the new bud arises at the anterior end 
from the midrib (Fig. 9, B), It comes either from the anterior cut- 
surface near the inner edge, or from the anterior end of the inner 
edge, and in some cases two new buds arise, one at each of these 
places. If the piece is removed from one side of the midrib it does 
not regenerate as quickly as when a part of the midrib is present, but 
when the new bud develops it arises from the anterior part of the 
inner edge (Fig. 9, B^), If the piece is cut far out at one side, it may 
be a long time before the new bud arises. This difference in the rate 
of development of these pieces is explained by Vochting as due to the 
simpler character of the cells near the midrib. 

If oblique pieces are cut off, with an anterior oblique cut-edge, as 
shown in Fig. 9, C, C^ the new bud arises along the anterior surface. If 
the piece includes a portion of the old midrib at its inner end, the new 
bud arises from this (Fig. 9, C\ but if the piece lies to one side of the 
midrib, the new bud arises near the anterior end of the anterior 
oblique surface (Fig. 9, C^ C^) 

A number of experiments that were made in order to determine 
what part gravity and light may take in the regeneration gave nearly 
negative results. The regeneration appears to result largely from 
internal factors. 

If a piece of the thallus is divided parallel to its surface, the two 
parts may each produce a new thallus, but this arises much more 
readily from the lower piece. If a piece of the latter is cut into 
small pieces no larger than half a cubic millimetre, and even much 
smaller, each may produce a new thallus. 

Vochting also studied the regeneration of parts having a limited 
growth. If a gemmiferous capsule is cut off, then split into two or 
four pieces, and these are placed on moist sand, it is found that new 
buds arise along the basal cut-edge. In order to show that this is 



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REGENERATION IN PLANTS 85 

not due to the new part arising on the basal end because there is no 
other cut-surface, the apical part of some of the pieces was cut off. 
These pieces, with two free ends, produced new buds only on their 
basal ends. 

The sexual organs of lunularia are borne on the top of erect 
reproductive branches having a limited growth (Fig. 9, D\ which 
carry later the sporiferous branches. The branches have a stalk and 
a terminal disk. If pieces of the stalk are cut off they do not pro- 
duce any new parts for a long time, but ultimately each produces 
from the basal cut-surface, or not far from the basal end, a new bud 
(Fig. E^), If the disk is left attached to the piece, the result is the 
same as before (Fig. D ^). If a twisted part of the stalk is used, new 
buds may develop at the base and also near the twisted region, as 
shown in Fig. 9, E^, If pieces of the stalk are stuck into the sand, 
some with the apical end, others with the basal end in the sand, the 
former produce new buds at the upper basal end, the latter produce 
buds on the stalk just above the surface of the sand. Pieces that 
retain the old disk when stuck into the sand (Fig. 9, Z>) produce one or 
more buds along the stalk above the sand, often some distance above 
it. The part buried in the sand does not seem able to develop new 
buds, and as a result they are produced at the first region of the 
basal part of the stalk, where the conditions make it possible for 
buds to develop. 

If the disk is cut entirely from the stalk and placed on moist 
sand, it produces adventitious buds in the region at which the stalk 
was removed. Buds are also produced at the bases of the rays that 
go off from the disk. They arise from the under side of the rays 
without regard to the position of the disk, i.e. whether it is turned 
upward or downward. If the rays are cut off they produce new 
buds at the base (Fig. 9, F\ and if the outer tip of the ray is also 
cut off, the new bud still arises at the base, as shown in Fig. 9, F^, 
These results on pieces with limited growth agree in every respect 
with those that have been obtained in flowering plants. Vochting 
thinks that the phenomenon is due in all cases to the limited growth 
of the parts. Goebel rejects this interpretation, and thinks that the 
results can be accounted for by the direction of the movement of 
formative or, at least, of building material. In favor of this view, 
he points out that in other liverworts the polarity is not shown in the 
same degree as in lunularia (according to Schostakowitsch), and 
also that in very old pieces of marchantia, as Vochting has shown, 
the polarity disappears. In the latter case the attractive action at 
the vegetative point, to which the building stuff is supposed to flow, 
is less strong ; and in longer pieces the influence of the apical region 
may not extend throughout the entire length of the thallus. In favor 

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86 REGENERATION 

of this interpretation he points out that in young prothallia of os- 
munda, adventitious shoots do not appear, but in older plants, that 
have become longer, these shoots may appear at the base, because 
this region is no longer influenced by the apex, and consequently it 
is possible for building material to accumulate at the basal end. 
It may be granted that Goebel's idea is possibly correct, viz. that the 
apex, or the apical end of a piece, may have some influence in pre- 
venting the development of shoots at the base, but it does not follow 
that this influence can be accounted for on the ground of a with- 
drawal of building stuff from the basal part. As I shall attempt to 
show in a later chapter, this influence may be of a different nature. 

It has been found by Pringsheim and others that pieces of the 
stem of mosses may also produce new plants, and this holds even for 
pieces of the stalk of the sporophore and of the wall of the spore 
capsule (Fig. lo, A-D). In this case, however, there is not produced 
a new moss plant directly from the end of the piece, but threads or 
protonemata grow out, as shown in Fig. lo. A, B, and from these 
new moss plants are formed in the same way as on the ordinary 
protonema. The threads that arise from the piece grow out from 
single cells in the middle part of the stem. These cells are less dif- 
ferentiated and are richer in protoplasm than are the other cells in 
the stem. 

The prothallia of certain ferns are said by Goebel to regenerate if 
cut in two ; at least this is true for the part that contains the vegeta- 
tive point. In a piece without the growing point, the cells are very 
little specialized, and the piece may remain alive ; yet it is incapable 
of producing a new growing, point. Comparing this result with the 
power of regeneration possessed by lower animals, Goebel states ^ that 
since in a plant new organs may arise without the typical form of the 
plant being produced, "therefore, the completion of a leaf, for instance, 
that has been injured, would ie of no use to the plant, while in ani- 
mals that do not have a vegetative point, the loss of an organ is a 
permanent disadvantage in case the organ removed cannot be regen- 
erated." The "explanation" of the difference in the two cases is 
supposed, apparently, by Goebel, to depend on the usefulness, or 
non-usefulness, of the regenerative act ! 

Brefeld has described several cases of regeneration in moulds. 
There is produced from the zygospore of Mucor mucedo a germinat- 
ing tube that forms at its end a single sporangium. If the tube is 
destroyed or injured, a second one is formed from the zygospore, and 
if this is injured a third time, a new tube is produced. Each time 
the sporangium is smaller than in the preceding case. 

If the spore-bearing stalk of Copriniis stercorarius is cut off, the 

1 Goebel, '98, page 37. 

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REGENERATION IN PLANTS 



87 



end grows out and produces a new sporangium. If pieces of the 
stem are cut off and placed in a nourishing medium, they produce 
from the ends a new mycelium, and from this new erect hyphae may 
develop. In the former case, the cut-end regenerates the part 
removed in somewhat the same way that an animal regenerates at the 
cut-end ; in the latter, there is a return to the mycelium stage, as in 




Fig. 36. — After Goebel. Achimenes Haaj^eana. A leaf-cutting of a plant in flower. The new 
plant, regenerating at base of leai-stalk, proceeded at once to produce a flower. 



the piece of the moss that produces a new protonema. If the my- 
celium and the protonema are looked upon as an embryonic stage in 
the formation of the sexual form, there is a return in these cases to an 
embryonic form or mode of development. 

One of the most remarkable and important discoveries in con- 
nection with the regeneration of plants is that the new individuals that 
develop from leaves cut off from certain plants differ acccq:ding to 

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88 REGENERATION 

the region of the old plant from which the leaf has been taken. 
Sachs discovered in 1893 that when the leaves of the begonia are 
taken from a plant in bloom, the adventitious buds that develop from 
the leaves very quickly produce new flowers. If the leaves are taken 
from a plant that has not yet produced flowers, the new plant that 
develops from the leaf does not produce flowers until after a much 
longer time. Goebel repeated the experiment with achimenes, and 
found that the new plants that develop from leaves from the flower- 
ing part of the stem (Fig. 36) produce flowers sooner than do the 
plants that develop from leaves from the base of the same plant. 
The former produce, as a rule, only one or two leaves and the flower 
stalk ; the latter, a large number of leaves. 

Sachs explains these results as due to a flower-forming stuff that 
is supposed to be present in the leaves when the plant is about to 
blossom. This material is supposed to act on the new plant that 
develops from the leaves, and to bring it sooner to maturity. Goebel 
points out that the result may also be explained by the fact that the 
leaves in the flowering region may be poorer in food materials and, 
in consequence, the adventitious buds that they produce are weaker, 
and, as experience has shown in other cases, a weakening of the 
tissues brings about more quickly the formation of flowers. Never- 
theless, Goebel inclines to Sachs' hypothesis of specific or formative 
stuffs, without, however, denying that there is also an inner polarity 
or "disposition" that also appears in the phenomena of regeneration. 
But Goebel seems to think that the phenomena of polarity "can 
most easily be brought under a common point of view by means of 
Sachs* assumption that there are different kinds of stuffs that go to 
make the different organs. In the normal life of the plant shoot- 
forming stuffs are carried to the vegetative points, while root-forming 
materials go to the growing ends of the roots. In consequence, 
when a piece is cut off and the flow of the formative stuffs is inter- 
rupted, the root-forming stuff will accumulate at the base of the 
piece and the shoot-forming stuffs at the apex. In the leaf the flow 
of all formative substances is toward the base of the leaf, and it is 
in this region that the new plants arise after the removal of the leaf." 
A confirmation of this point of view, Goebel believes, is furnished by 
the following cases. Some monocotyledonous plants seldom set seed 
because the vegetative organs, the bulbs, tubers, etc., that reproduce 
the plant, exert a stronger attraction upon the building stuff than 
do the young seeds. ^ Lindenmuth has shown in some of these 
forms that pieces of the stem produce, near the base, numerous 
bulblets, because the building stuff moves toward the base. In 
Hyacintlms orientalis, on the other hand, bulblets are produced at 

* Examples of this are found in Lilium candidum^ Lachenalia luUola, 

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REGENERATION IN PLANTS 89 

the apical part of a piece of the flowering plant. In this plant the 
seeds ripen normally, presumably because of the migration of stuffs 
toward the developing seeds. The results in all these cases are due, 
Goebel thinks, to the direction of the flow of formative stuffs, and 
cannot be explained as connected in any way with the limited 
growth of the part. 

These cases, cited by Goebel, are not in my opinion altogether to 
the point; and they fail also to establish convincingly the conclusion 
that Goebel draws from them. It may be granted that starch is 
stored up in certain parts of the plant, and if these parts are re- 
moved the starch may be stored up in other parts, as Vochting 
(*87) has shown ; but that the movement of this starch to the base 
can account for the lack of development of the seeds in certain cases 
seems to me improbable, or, at least, far from being established by 
the cases cited. It may be granted that the presence of starch in a 
region may act on the organs there present and determine their fate. 
Vochting has shown in the potato that by removing the tubers the 
axial buds, especially in the basal leaves, become tuber-like bodies, 
but it should not be overlooked that the tubers themselves are formed 
from underground stolons, that arise in the same way as do those 
in the axils of the leaves. It would be erroneous, I think, to con- 
clude from these cases of the effect of food stuffs on certain re- 
gions that there are formative stuffs for all the organs of the plant, 
and that these stuffs migrate in different directions and determine 
the nature of the part Even the migration of such substances in 
definite directions in the tissue is itself in need of explanation, since 
it has been made highly probable by Vochting's experiments that 
this is not produced by agents outside of the plant. Furthermore, 
Vochting has shown that the tendency of starch to accumulate in the 
tubers and the formation of the tuber are separate phenomena. 

This hypothesis of formative stuffs held by such able botanists 
as Sachs and Goebel demands nevertheless serious consideration, if 
for no other reason than that if it is true it offers quite a simple 
explanation of many phenomena of growth and of regeneration. We 
should, I think, distinguish between specific or formative stuffs and 
building or food stuffs. By specific stuffs is meant a special kind of 
substance which, being present in a part, determines the nature of the 
part. Sachs supposes, for instance, that a specific substance is made 
by the leaves of a plant which is transported to the vegetative, growing 
region (which has so far produced only leaves), and changes its 
growth so that flowers are produced. Goebel does not commit him- 
self altogether to specific stuffs of this sort, but speaks also of 
building stuffs. By building stuff we may understand food material 
that is necessary for growth, and from which any part of the plant 

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90 REGENERATION 

may be made. Its presence in larger or smaller quantities may 
determine what a particular part shall become, but further than 
this it exerts no specific action. This means that the presence of a 
certain amount of food substance may determine what a given region 
shall produce, but it is not supposed that there are different kinds of 
food materials that correspond to each kind of structure. If there 
were such, they would not differ from specific substances, unless we 
wish to make subtle distinctions without any basis of fact to go upon. 

Goebel points out that there is evidence to show that the greater 
or less quantity of food substance contained in a plant often deter- 
mines the nature of its growth, as for instance the production of 
flowers when the food supply runs low and the production of foliage 
when the food supply is abundant. This difference may explain 
Sachs' experiment with begonia leaves ; and if so, there is no need 
for supposing specific flower stuffs to be made in the plant. 

There is another point of view which has been, I think, too much 
neglected, viz. that the production of food stuffs is itself an expression 
of changes taking place in the living tissues, and if the structure 
is changed so that it no longer produces the same substances it 
may then lead to the development of different kinds of organs. The 
difference in the regeneration of an apical and a basal leaf of begonia 
may be due to some difference in the structure of the protoplasm. 
The greater or smaller amount of starch produced in these leaves may 
be only a measure of, and not a factor in, the result. 

In this same connection another question needs to be discussed. 
It is assumed by several botanists that in a normal plant the latent 
shoots or buds along the stem do not develop so long as the terminal 
shoots are growing, because the latter use up all the food material 
that is carried to that region. If the terminal bud is destroyed the 
lateral shoots then burst forth, in consequence, it is assumed, of the 
excess of food stuff that now comes to them. I do not believe that 
the phenomena can be so easily explained. If a piece of a plant is 
cut off, the leaves removed, and the piece suspended in a moist 
chamber and kept in the dark, the lateral buds at the apex will begin 
to develop. If we assume that the piece cannot develop any new 
food substance in the dark, then it contains just the same amount 
as it did while a part of the plant, and yet that amount is ample for 
the development of the lateral buds. Moreover, only the more apical 
buds develop ; but if the piece is then cut in two, the apical buds of 
the basal piece, that had remained undeveloped, will now develop. 
How can this be explained by the amount of food substances in the 
piece } If it is assumed that in the normal plant the food substances 
flow only to the growing points, and the buds are out of the main cur- 
rent and fail in consequence to develop, it can be shown that this 

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REGENERATION IN PLANTS 9 1 

idea also fails to explain certain results. Vochting has found, for 
example, that if an incision is made below a bud and the piece con- 
taining the bud be lifted up somewhat from the rest of the piece, 
remaining attached only at its anterior end, the bud will begin to 
develop. In this case the conditions preclude an accumulation of food 
substances in the piece, and the bud is even farther removed than at 
first from the main current, yet it begins to develop. 

We shall find, I think, that the idea of food stuffs fails to explain 
some of the simplest phenomena, and while it need not be denied 
that under certain conditions the presence or accumulation of food 
materials may produce certain definite results, yet such food stuffs 
seem to play a very subordinate part as compared with certain other 
internal or innate factors. 



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CHAPTER V 
REGENERATION AND LIABILITY TO INJURY 

There is a widespread belief amongst zoologists that a definite 
relation exists between the liability of an animal to injury and its 
power of regeneration. It is also supposed that those individual 
parts of an animal that are more exposed to accidental injury, or to 
the attacks of enemies, are the parts in which regeneration is best 
developed, and conversely, that those parts of the body that are rarely 
or never injured do not possess the power of regeneration. 

Not only do we find this belief implied in many ways, but we find 
this point of view definitely taken by several eminent writers, and in 
some cases carried so far that the process of regeneration itself is sup- 
posed to be accounted for by the liability of the parts to injury. In 
order that it may not appear that I have exaggerated the widespread 
occurrence of this belief, a few examples may be cited. 

Reaumur in 1742 pointed out that regeneration is especially char- 
acteristic of those animals whose body is liable to be broken, or, as in 
the earthworm, subject to the attacks of enemies. Bonnet (1745) 
thought that such a connection exists as has just been stated, and 
that the animals that possess the power of regeneration have been 
endowed with germs set aside for this very purpose. He further 
believed that there would be in each animal that regenerates as many 
of these germs as the number of times that it is liable to be injured 
during its natural life. Darwin in his book on Animals and Plants 
under Domestication says : " In the case of those animals that may 
be bisected, or chopped into pieces, and of which every fragment will 
reproduce the whole, the power of regrowth must be diffused through- 
out the whole body. Nevertheless, there seems to be much truth in 
the view maintained by Professor Lessona^ that this capacity is gen- 
erally a localized and special one serving to replace parts which are 
eminently liable to be lost in each particular animal. The most strik- 

1 Delage and Giard give Lessona ('69) the credit for first stating that the phenomenon 
of regeneration is an adaptation to liability to injury; but Reaumur first suggested this idea 
in 1742, and Bonnet in 1745. Delage's interpretation, viz. that Lessona ascribed this to 
a prevoyance de la nature^ has been denied by I^ssona*s biographer, Camerano {^La Ft/a 
di M, /.essona^ Acad, A', d, Torino^ 2, XLV, 1896), and by Giard {Sur Vautotomie Para- 
sifaire, etc., CompL Rendm de Seances de la SociHe de Biologie^ May, 1897). 

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REGENERATION AND LIABILITY TO INJURY 93 

ing case in favor of this view is that the terrestrial salamander, accord- 
ing to Lessona, cannot reproduce lost parts, whilst another species 
of the same genus, the aquatic salamander, has extraordinary powers 
of regrowth, as we have just seen ; and this animal is eminently liable to 
.have its limbs, tail, eyes, and jaws bitten off by other tritons." 

Lang, referring to the brittleness of the tails of lizards, points out 
that this is a very useful character, since the bird of prey that has 
struck at a lizard gets hold of only the last part of the animal to dis- 
appear under cover ; the lizard escapes by breaking off its tail. The 
brittleness of the tail is, therefore, an adaptive character that has 
become fixed by long inheritance. 

To this example may be added that of certain land snails in the 
Philippine Islands. The individuals of the genus helicarion live on 
trees in damp forests, often in great droves. They are very active, 
and creep with unusual swiftness over the stems and leaves of the 
trees. Semper has recorded that all the species observed by him 
have the remarkable power of breaking off the tail (foot) close behind 
the shell, if the tail is roughly grasped. A convulsive movement is 
made until the tail comes off, and the snail drops to the ground, where 
it is concealed by the leaves. Semper adds that in this way the snails 
often escaped from him and from his collectors, leaving nothing behind 
but their tails. The tail is said to be the most obvious part of the 
animal, and it is assumed that this is, therefore, the part that a rep- 
tile or bird would first attack.^ Lang states that in this case external 
influences have produced an extraordinarily well-developed sensitive- 
ness in the animal, so that it reacts to the external stimulus by volun- 
tarily throwing off the tail. It would be, of course, of small advantage 
to be able to throw off the tail unless the power of regenerating the 
lost organ existed, or was acquired at the same time as the extreme 
sensitiveness that brings about the reaction. Lang does not state, 
however, explicitly that he believes the regenerative power to have 
arisen through the exposure of the tail of the lizard and the tail of 
the snail to injury, although he thinks that the mechanism by means 
of which these parts are thrown off has been acquired in this way. 
Several other writers have, however, used these same cases to illus- 
trate the supposed principle of liability to injury and power of 
regeneration. 

Weismann in his book on The Germ Plasm has adopted the 
principle of a connection between regeneration and liability to in- 
jury and has carried it much farther than other writers. We can, 
therefore, most profitably make a careful examination of Weismann's 

^ Whether, having once failed in this way to obtain the snail, the bird or lizard would 
not learn to make a frontal attack is not stated. Or shall we assume that the tail is all that 
is wanted? ^.-^ , 

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94 REGENERATION 

position. His general idea may be gathered from the following 
quotation : ^ " The dissimilarity, moreover, as regards the power of 
regeneration in various members of the same species^ also indicates that 
adaptation is an important factor in the process. In proteus, which in 
other respects possesses so slight a capacity for regeneration, the gills 
grow again rapidly when they have been cut off. In lizards again this 
power is confined to the tail, and the limbs cannot become restored. 
In these animals, however, the tail is obviously far more likely to 
become mutilated than are the limbs, which, as a matter of fact, are 
seldom lost, although individuals with stumps of legs are occasionally 
met with. The physiological importance of the tail of a lizard con- 
sists in the fact that it preserves the animal from total destruction, for 
pursuers will generally aim at the long trailing tail,^ and thus the 
animal often escapes, as the tail breaks off when it is firmly seized. 
It is, in fact, as Leydig was the first to point out, specially adapted for 
breaking off, the bodies of the caudal vertebrae from the seventh 
onward being provided with a special plane of fracture so that they 
easily break into two transversely. Now if this capability of fracture 
is provided for by a special arrangement and modification of the parts 
of the tail, we shall not be making too daring an inference if we 
regard the regenerative power of the tail as a special adaptation^ pro- 
duced by selection, of this particular part of the body, the frequent loss 
of which is in a certain measure provided for, and not as the outcome 
of an unknown * regenerative power ' possessed by the entire animal 
This arrangement would not have been provided if the part had been 
of no, or of only slight, physiological importance, as is the case in 
snakes and chelonians, although these animals are as highly organized 
as lizards. The reason that the limbs of lizards are not replaced is, I 
believe, due to the fact that these animals are seldom seized by the 
leg, owing to their extremely rapid movements." Overlooking the 
numerous cases of the regeneration of internal organs that have been 
known for several years, and basing his conclusion on a small, uncon- 
vincing experiment of his own on the lungs of a few salamanders, 
Weismann concludes : " Hence there is no such thing as a general 
power of regeneration ; in each kind of animal this power is graduated 
according to the need of regeneration in the part under consideration ; 
that is to say, the degree in which it is present is mainly in proportion 
to the liability of the part to injury." 

After arriving at this conclusion the following admission is a 
decided anticlimax : " The question, however, arises as to whether 
the capacity of each part for regeneration results from special process 
of adaptation, or whether regeneration occurs as the mere outcome — 

1 The Gi^m Plasm, Translation by W. Newton Parker, 1893, P^S* ^^^^ 

3 There are no facts that show that this statement is not entirely imaginar>-. T. H. M. 

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REGENERATION AND LIABILITY TO INJURY 95 

which is to some extent unforeseen — of the physical nature of an 
animal. Some statements which have been made on this subject seem 
hardly to admit of any but the latter explanation." After showing that 
some newts confined in aquaria attacked each other, "and several 
times one of them seized another by the lower jaw, and tugged and 
bit at it so violently that it would have been torn off fiadi not separated 
the animals,''^ and after referring to the regeneration of the stork's 
beak, Weismann concludes: "Such cashes, the accuracy of which can 
scarcely be doubted, indicate that the capacity for regeneration does not 
depend only on the special adaptation of a particular organ, but that ' 
a general power also exists which belongs to the whole organism, and 
to a certain extent affects many and perhaps even all parts. By 
virtue of this power, moreover, simple organs can be replaced when 
they are not specially adapted for regeneration." The perplexity of 
the reader, as a result of this temporary vacillation on Weismann's 
part, is hardly set straight by the general conclusion that follows on 
the same page : " We are, therefore, led to infer that the general 
capacity of all parts for regeneration may have been acquired by 
selection in the lower and simpler forms, and that it gradually 
decreased in the course of phylogeny in correspondence with the 
increase in complexity of organization ; but that it may, on the other 
hand, be increased by special selective processes in each stage of its 
degeneration, in the case of certain parts which are physiologically 
important and are at the same time frequently exposed to loss." 

There are certain statements of facts in the same chapter that are 
incorrect, and the argument is so loose and vague that it is difficult 
to tell just what is really meant. As a misstatement of fact I may 
select the following case : It is stated that lumbriculus does not have 
the power of regenerating laterally if cut in two, and it is argued that 
a small animal of this form could rarely be injured at the side without 
cutting the animal completely in two. As a matter of fact, lumbricu- 
lus can regenerate laterally, and very perfectly, as any one can verify 
if he takes the trouble to perform the experiment ; but, of course, if 
the whole animal is split in two lengthwise the pieces die, or if a very 
long piece is split from one side the remaining piece usually disin- 
tegrates. If, however, the anterior end is split in two for a short 
distance, or if a piece is partially split in two, the half remaining in 
contact with the rest of the piece completes itself laterally. The 
same result follows also in the earthworm. 

As an example of looseness of expression I may quote the follow- 
ing from Weismann: "A useless or almost useless rudimentary part 
may often be injured or torn off without causing processes of selection 
to occur which would produce in it a capacity for regeneration. The 
ifhe italics are, of course, my own. T. H. M. 

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96 REGENERATION 

tail of a lizard again, which is very liable to injury, becomes regen- 
erated because, as we have seen, it is of great importance to the indi- 
vidual and if lost its owner is placed at a disadvantage." And as an 
example of vagueness, the following statement commends itself: 
'* Finally the complexity of the individual parts constitutes the third 
factor which is concerned in regulating the regenerative power of the 
part in question ; for the more complex the structure is, the longer 
and the more energetically the process of selection must act in order 
to provide the mechanism of regeneration, which consists in the 
equipment of a large number of different kinds of cells with the sup- 
plementary determinants which are accurately graduated and regu- 
lated as regards their power of multiplication." 

Without attempting to disentangle the ideas that are involved in 
these sentences, let us rather attempt to get a general conception of 
Weismann's views. In a later paper (1900), in reply to certain criti- 
cisms, he has stated his position somewhat more lucidly. In the 
following statement I have tried to give the essential part of his 
hypotheses: Weismann believes the process of regeneration to be 
regulated by "natural selection " ; in fact, he states that it has arisen 
through such a process in the lower animals — since they are more 
subject to injury — and that it has been lost in the higher forms 
except where, on account of injury, it has been retained in certain 
parts. Thus when Weismann speaks of regeneration as being an 
adaptation of the organism to its environment, we must understand 
him to mean that this adaptation is the result of the action of natural 
selection. We should be on our guard not to be misled by the state- 
ment that because regeneration is useful to the animal, it has been 
acquired by natural selection, since it is possible that regeneration 
might be more or less useful without in any way involving the idea 
that natural selection is the originator of this or of any other adapta- 
tion. It will be seen, therefore, that in order to meet Weismann on 
his own ground it will be necessary to have a clear understanding in 
regard to the relation of regeneration to Darwin's principle of natural 
selection. With Weismann*s special hypothesis of the "mechanism," 
so-called, by which regeneration is made possible we have here noth- 
ing to do, but may consider it on its own merits in another chapter. 

In order to have before us the material for ar discussion of the 
possible influence of natural selection on regeneration, let us first 
examine the facts that bear on the question of the liability of the 
parts to injury and their power to regenerate, and in this connection 
the questions concerning the renewal of parts that are thrown off by 
the animals themselves in response to an external stimulus are worthy 
of careful consideration. A comparison between the regeneration of 
these parts with that of other parts of the same animal gives also 

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REGENERATION AND LIABILITY TO INJURY 97 

important data. Furthermore, a comparison may be made between 
different parts of the same animal, or between the same parts of 
different animals living under similar or dissimilar conditions. 

There are only a few cases known in which a systematic exami- 
nation has been carried out of the power of regeneration of the dif- 
ferent parts of the body of the same animal. Spallanzani's results 
show that those salamanders that can regenerate their fore legs can 
regenerate their hind legs also. Towle, who has examined in my 
laboratory the regeneration of a number of American newts and sala- 
manders, finds also that both the fore and hind legs regenerate in the 
same forms. The tail and the external gills, in those newts with 
gills, also regenerate. It has also been shown in triton that the eye 
regenerates if a portion of the bulb is left. Broussonet first showed 
(1786) that the fins of fish have the power to regenerate, although, 
strangely enough, Fraisse and Weismann state that very little power 
of regeneration is present in the fins of fish. I have found that the 
fins of several kinds of fish regenerate, belonging to widely different 
families.^ In Fiindulus heteroclitus I have found that the pectoral, 
pelvic, caudal, anal, and dorsal fins have the power of regeneration. 
In reptiles the feet do not regenerate, — at least no cases are known, — 
but the tail of lizards has this power well developed. In birds neither 
the wings nor the feet regenerate, but Fraisse has described the case 
of a stork in which, the lower jaw being broken off, and the upper 
being cut off at the same level, both regenerated. Bordage has 
recorded the regeneration of the beak of the domesticated fighting 
cocks (of the Malay breed) of Mauritius. In the mammals neither 
the legs, nor the tail, nor the jaws regenerate, although several of 
the internal organs, as described in the next chapter, have extensive 
powers of regeneration. 

The best opportunity to examine the regenerative power in simi- 
lar organs of the same animal is found in forms like the Crustacea, 
myriapods, and insects, in which external appendages are repeated in 
each or many segments of the body. In decapod Crustacea, includ- 
ing shrimps, lobsters, crayfish, crabs, hermit-crabs, etc., regeneration 
takes place in the walking legs of all the forms that have been exam- 
ined, and this includes members of many genera and families. I have 
made an examination of the regeneration of the appendages (Fig. 37) 
of the hermit-crab. In this animal, which lives in an appropri- 
ated snail's shell, only the anterior part of the body projects from the 
shell. The part that protrudes is covered by a hard cuticle, while the 
part of the body covered by the shell is quite soft. Three pairs of 
legs are protruded from the shell. The first pair with large claws 

^ Fundulus heteroclitus^ Stenopus chrysops^ Decapterm macrella^ Menticirrhus macreiia, 
Carassim auratuSf Phoxinus funduloideSy Noturm sp.^ anl a few others. 

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98 



REGENERATION 



are used for procuring food, and as organs of offence and defence ; 
the second and third pairs are used for walking. The following two 
pairs, that correspond to the last two pairs of walking legs of crabs 
and crayfishes, are small, and are used by the animal in bracing it- 
self against the shell. The first three pairs of legs have an arrange- 




FlG. 37. — Appendages of Hermit-crab {Eupagurus longlcarpus) . A. Third walking leg. B. Next 
to last thoracic leg. /?i. Last thoracic leg. C 6*1, CK Three abdominal appendages of male. 
D. Tclson and sixth segment with last pair of abdominal appendages. E. Regeneration of 
new leg from cut-end outside of " breaking-joint." F. Leg regenerating from cut made inside 
of " breaking-joint." G. Leg regenerating from cut made very near the body. 

ment at the base, the "breaking-joint," by means of which the leg is 
thrown off, if injured. The last two pairs of thoracic legs cannot be 
thrown off. The first three pairs of legs are often lost under natural 
conditions. In an examination of i88 individuals I found that 21 (or 
II per cent) had lost one or more legs. If one of the first three legs 
is injured, except in the outer segment, it is thrown off at the break- 
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REGENERATION AND LIABILITY TO INJURY 99 

ing-joint, and a new leg regenerates from the broken-off end of the 
stump that is left. The new leg does not become full size, and is of 
little use until the crab has moulted at least once. The leg breaks 
off so close to the body, and the part inside of the breaking-joint is 
so well protected by the bases of the other legs, that it is scarcely 
possible that the leg could be torn off inside of the breaking-joint, 
and, as a matter of observation, all crabs that are found regenerating 
their legs under natural conditions do so from the breaking- joint. 
If, however, by means of small scissors, the leg is cut off quite near 
the body, a new leg regenerates from the cut-end, even when the leg 
is cut off at its very base. The breaking-joint would thoroughly pro- 
tect from injury the part of the leg that lies nearer to the body, and 
yet from this inner part a new leg is regenerated. Moreover, the 
new leg is perfect in every respect, even to the formation of a new 
breaking-joint. In this case we have a demonstration that there need 
be no connection between the liability of a part to injury and its 
power of regeneration. 

In still another way the same thing may be shown. If the crab 
is anaesthetized, and a leg cut off outside of the breaking-joint, it is 
not, at the time, thrown off — the nervous system, through whose 
action the breaking off takes place, being temporarily thrown out 
of order. After recovery, although the leg is thrown off in a large 
number of cases, it is sometimes retained. In such cases it is found 
that from the cut-end the missing part is regenerated. In this case 
also we find that regeneration takes place from a part of the leg that 
can never regenerate under natural circumstances. 

The third and fourth legs of the hermit-crab cannot be thrown 
off, but they have the power of regeneration at any level at which 
they may be cut off. They are in a position where they can seldom 
be injured, and I have never found them absent or injured in crabs 
caught in their natural environment. The soft abdomen is protected 
by the snaiFs shell. At the end of the abdomen the last pair of 
abdominal appendages serve as anchors to hold the crab in the shell. 
These appendages are large and very hard, and can seldom be in- 
jured unless the abdomen itself is broken, and under these circum- 
stances the crab dies. Yet if these appendages are cut off they 
regenerate perfectly, and after a single moult cannot be distinguished 
from normal ones. 

The more anterior abdominal appendages are present only on one 
side of the adult, although they are present on both sides of the larva, 
and, to judge from a comparison with other Crustacea, these append- 
ages have degenerated completely on one side, and have become 
rudinientary in the male, even on the side on which they are present. 
They too will regenerate if they are cut off. In the female these 

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I CX) REGENERA TION 

appendages are used to carry the eggs, and are, therefore, of use. 
They also have a similar power of regeneration. The maxillae and 
maxillipeds of the hermit-crab have likewise the power of regenera- 
tion, as have also the two pairs of antennae and the eyes. 

In other decapod Crustacea also it has been shown that the power 
of regeneration of the appendages is well developed. It has been 
long known that the crayfish and the lobster can regenerate lost 
parts. The first pair of legs, or chelae, in these forms has a breaking- 
joint, at which the leg can be thrown off, yet in the crayfish I have 
seen that if the leg is cut off inside of the breaking-joint it will regen- 
erate. The four pairs of walking legs do not possess a breaking-joint, 
but may be thrown off in some cases at a corresponding level. They 
regenerate from this level, as well as nearer the body and farther be- 
yond this region. Przibram has recently shown that, in a number of 
Crustacea, regeneration of the appendages takes place, even when the 
entire leg is extirpated as completely as possible. 

Newport has shown that the myriapods can regenerate their legs, 
and it is known that several forms have the power of breaking off 
their legs in a definite region at the base if the legs are injured, and 
I have observed in Cermatia forceps that this takes place even when 
the animal is thrown into a killing fluid. Newport ('44) has also 
shown that when the legs of a caterpillar are cut off new ones regen- 
erate during the pupa stage. It has been long known ^ that the legs 
of mantis can regenerate, and Bordage, who has recently examined 
the question more fully, has shown that a breaking-joint is present at 
the base of the leg. The tarsus of the cockroach also regenerates, 
producing only four, instead of the five, characteristic segments.* 

A number of writers have recorded the regeneration of the legs of 
spiders.^ Schultz, who has recently examined more thoroughly the 
regeneration of the legs in some spiders, finds that the leg is renewed 
if cut off at any level. He reqioved the leg most often at the meta- 
tarsus, but also at the tibia, and generally between two joints. In 
some cases the leg was cut off at the coxa, at which level it is gen- 
erally found to be lost under natural conditions. Wagner observed 
in tarantula that when the leg is removed at any other place than at 
the coxa, the animal brings the wounded leg to its jaws, and bites it 
off down to the coxa. In the EpeuidcB, that Schultz chiefly made use 
of, this never happened. He observed, however, even in these forms, 
that when the leg is cut off at the coxa it regenerates better than 

1 See Newport and Scudder. 

2 Brindley, '97. 

' Lepelletur, Nouveau Bulletin de la Societe philomaHque^ 1813, Tome Til, page 254 ; 
Heineken, ZooL Journal, 1828, Vol. IV, page 284 (also for insects, ibiit^ page 294) ; 
Miiller, Afanual de Physiol^ Tome I, page 30 ; Wagner, W., Bull. Soc, Imp. Natural.^ 
Moscow, '87. 



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REGENERATION AND LIABILITY TO INJURY 



lOI 



when cut off at any other level. Schultz states that we see here an 
excellent example of how regeneration is influenced by natural selec- 
tion, since regeneration takes place best where the leg is most often 
broken off. On the other hand, the author hastens to add that since 
regeneration also takes place when the leg is cut off at any other 



^^^x) 



^- \ 












Fig. 38. — A-F. After King. A. Starfish with four arms regenerating at different levels. B. Three 
arms regenerating from disk. C. Arm split jn two producing two arms. D. Arm cut off 
obliquely, regenerating at right angles to cut-surface. E. Starfish split between two aims, 
producing two new arms from split. E. An arm, with a small piece of disk attached, regen- 
erating three new arms. G. After P. and F. Sarasin. Starfish {Linckia multiformis) with 
four new arms springing from end of one arm. Interpreted as a new starfish, but probably 
only multiple arms (see C, above). 

level, this shows that the power to regenerate is characteristic of all 
parts of the organism, and is not merely a phenomenon of adaptation, 
as Weismann believes. It seems highly improbable that a spider 
could ever lose a leg in the middle of a segment, i,e, between two 
joints, since the segments are hard and strong and the joints much 

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I02 REGENERATION 

weaker; but nevertheless the leg has the power to regenerate also 
from the middle of the segment, if cut off in this region. 

The formatipn of the new part takes place somewhat differently, 
according to Schultz, when the leg is amputated between two seg- 
ments than when cut off at the coxa. In the latter case, there is pro- 
duced from the cut-end of the last segment a solid rod which, as it 
grows longer, bends on itself several times. Joints appear in the 
rod, beginning at the base. The leg is set free at the next moult. 
If the leg is cut off nearer the distal end a smaller rod is formed, 
that extends straight forward, or may be thrown into a series of folds. 
It lies, however, inside of the last segment, since the surface exposed 
by the cut is quickly covered over by a chitinous covering. The piece 
is set free at the next moult. 

Loeb has found that if the body of the pycnogonid, Phoxichili- 
dium niaxillare, is cut in two there regenerates from the posterior 
end of the anterior half a new body-like outgrowth. 

Without attempting to describe the many cases in worms and 
moUusks in which there is no obvious connection between the power 
of the part to regenerate and its liability to injury, but where it is 
more difficult to show that it may not exist, let us pass to an examina- 
tion of the regeneration of the starfish. It has been known since the 
time of Reaumur that starfish have the power of regenerating new 
arms if the old ones are lost. It has been stated that in certain 
starfishes an arm itself can produce a new starfish, — Haeckel C78), 
P. and R. Sarasin ('88), von Martens ('84), and Sars ('75, — but this 
has been denied by other observers. In several species of starfishes, 
the separated arm does not regenerate ; but if a portion, even a small 
piece, of the disk is left with the arm, a new disk and arms may 
develop (Fig. 38, F\ When the arm of Asterias vulgaris is injured 
it pinches off in many cases at its base, and a new arm grows out from 
the short stump that remains. When these starfishes regenerate 
new arms in their natural environment, the new arms almost always 
arise from this breaking region.^ Thus King found out of 1914 
individuals of Asterias vulgaris collected at random, 206, or 10.7 
per cent, had one or more new arms, and all these except one arose 
from near the disk. In other species it appears that the outer por- 
tions of the arm may be broken off without the rest of the arm being 

* The Sarasins have described several cases in Linckia multiformis in which an old arm 
has one or more new arms arising from it. In one case (copied in our Fig. 38, C7), four rays 
arise from the end of one arm, producing the appearance of a new starBsh. In fact the 
Sarasins interpret the result in this way, although they state that there is no madreporite on 
the upper surface, and they did not determine whether a mouth is formed at the convergence 
of the rays, because they did not wish to destroy so unique a specimen — even to find out 
the meaning of it. There seems to me little probability that the new structure is a starfish, 
but the old arm has been so injured that it has produced a number of new arms. 



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REGENERATION AND LIABILITY TO INJURY IO3 

thrown off. King has found that in asterias, regeneration takes place 
more rapidly from the base than at a more distal level. It may 
appear, at first thought, that the more rapid regeneration of the arm 
at the place at which it is usually thrown off may be associated with 
its more frequent loss at this region — in other words, that the more 
rapid regeneration has been acquired by the region at which the arm 
is generally broken off. This interpretation is, however, excluded by 
the fact that, in general, the nearer to the base the arm is cut off, so 
much the more rapid is its regeneration. In other words, the more 
rapid regeneration of the arm at the base is only a part of a general 
law that holds throughout the arm. If the proposition is reversed, 
and it is claimed that the arm has acquired the property of breaking 
off at the base, because it regenerates more rapidly at that level, the 
following fact recorded by King is of importance, viz. that, although 
the arm regenerates faster at the base, yet a new arm is not any 
sooner produced in this way, since there is more to be produced and 
the new arm from the base may never catch up to one growing less 
rapidly from a more distal cut-surface, but having a nearer goal to 
reach. 

The results of our examination show that those forms that are 
liable to have certain parts of their bodies injured are able to regener- 
ate not only these parts, but at the same time other parts of the body 
that are not subject to injury. The most remarkable instance of this 
sort is found in those animals having breaking-joints. In these 
forms, we find that regeneration takes place both proximal and distal 
to this region. If the power of regeneration is connected with the 
liability of a part to injury, this fact is inexplicable. 

Turning now to the question as to whether regeneration takes 
place in those species that are subject to injury more frequently or 
better than in other species, we find that the data are not very com- 
plete or satisfactory for such an examination. It is not easy to ascer- 
tain to what extent different animals are exposed to injury. If we 
pass in review the main groups of the animal kingdom, we can at 
least glean some interesting facts in this connection. 

In the protozoa nucleated pieces have been found to regenerate 
in all forms that have been examined, including amoeba, difflugia, 
thalassicolla, paramcecium, . stentor, and a number of other ciliate 
infusoria. 

In the sponges it has been found by Oscar Schmidt that pieces 
may produce new individuals, but how widely this occurs in the group 
is not known. In the coelenterates many forms are known to regen- 
erate, and it is not improbable that in one way or another the process 
occurs throughout the group. The hydroid forms, hydra, tubularia, 
parypha, eudendrium, antennularia, hydractinia, podocorvije, etc.. 

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I04 REGENERATION- 

the jelly-fish, gonionemus, and certain members of the family Thau- 
mafitidcey have been found to regenerate. Amongst the Scyp/iosoa^ 
metridium, cerianthus, and the scyphistoma of aurelia regenerate, 
and the jelly-fishes belonging to this group have a limited amount of 
regenerative power. 

In the platodes we find that all the triclads, thus far examined, 
including planaria, phagocata, dendrocoelum, and the land triclad, 
bipalium, regenerate. It has been shown that the marine triclads 
also regenerate, but less rapidly and extensively, while the marine 
polyclads have very limited powers of regeneration. The regeneration 
of the trematodes and cestodes has not, so far as I know, been studied, 
neither have the nematodes been examined from this point of view. 

Some of the neraerteans regenerate, others do not seem to have 
this power. A small fresh-water form, tetrastemma, that I examined, 
did not regenerate, although some of the pieces, that were filled with 
eggs, remained alive for several months. 

In the annelids we find a great many forms that regenerate — 
many marine polychaeta have this power; all oligochaeta that have 
been studied regenerate ; both land forms, like lumbricus, allolobo- 
phora, etc., and fresh-water forms, like lumbriculus, nais, tubifex, etc. 

In the Crustacea the appendages have the power to regenerate in 
all the forms that have been examined. 

Several kinds of myriapods, as well as a number of spiders, are 
known to regenerate their legs. In the insects, however, only a few 
forms are known to have this power, — caterpillars, manjtis, and the 
cockroach. The large majority of insects, in the imago state, do not 
seem to be able to regenerate, although in a few cases regeneration 
has been found to occur. ^ 

In the mollusks, regeneration of the head takes place under certain 
conditions. Spallanzani thought that if the entire head is cut off a 
new one regenerates. This conclusion was denied by at least eleven 
of his contemporaries, and confirmed by about ten others. It was 
found later that the result depends in part on the time of year and in 
part on the kind of snail. Carri^re, who more recently examined the 
question, found that even under the most favorable conditions regen- 
eration does not take place if the circumoesophageal nerve-commissure 
is completely removed with the head, but if a part remains, a new 
head develops. It has been stated that a new foot regenerates in 
helicarion, and I have found that the foot regenerates also in the fresh- 
water snails, physa, limnaea, and planorbis. If the margin of the 
shell of a lamellibranch or of a snail is broken off, it is renewed by 
the mantle. The arms of some of the cephalopods are known to 
regenerate, particularly the hectocotylized arm. 

1 For a review of the literature see Brindley, '98. ^->. j 

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REGENERATION AND LIABILITY TO INJURY 



105 



In all the main groups of echinoderms, with one possible excep- 
tion, regeneration has been found to take place. Probably all star- 
fishes and brittle-stars regenerate their arms, and even if cut in two 
or more pieces, new starfishes develop. The crinoids regenerate lost 
arms, and even parts of the disk ; also the visceral mass. The holo- 
thurians have very remarkable powers of regeneration. In some 
forms regeneration takes place, if .the animals are cut in two, or even 
in more than two pieces. The remarkable phenomenon of eviscera- 
tion that take place in certain holothurians, if they are roughly 
handled, or kept under unfavorable conditions, are well known and 
have been described by a number of writers. It has even been sug- 
gested that the holothurian may save itself by offering up its viscera 



c 




B 




Fig. 39. — /^. Amphiuma means with left fore and hind leg regeneraring. B, Neciurus maculatvs 
with right fore Ifg beginning to regenerate after eight months. C PUthedon cinereus. A, 
By C. r>rawn to same scale. 

to its assailant ! Unfortunately for this view, it has been found that 
the viscera are unpalatable, at least to sea-anemones and to fishes. 
Ludwig and Minchin suggest that the throwing off of the Cuvierian 
organs, which are attached to the cloaca, is a defensive act, and if car- 
ried too far, according to the latter writer, the viscera may also be 
lost. The holothurians have remarkable recuperative powers and 
may regenerate new viscera in a very short time. The sea-urchins 
form, perhaps, an exception in this group, since there are no records 
of their regenerative power, but no doubt this is because they have 
not been as fully investigated as have other forms. 

In the vertebrates tjie lower forms, amphioxus, petromyzon, and 
sharks, have not been studied in regard to their regenerative power. 

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I06 REGENERATION 

In the teleostean fishes the fins of a number of forms are known to 
regenerate. It is probable that this takes place in most members of 
the group. 

In the amphibia we find a large number of forms that regenerate 
their limbs and tail, and other parts of the body, but limitations appear 
in certain forms. The rapid regeneration of the legs in the smaller 
urodeles has been often described. In larger forms it takes place 
more slowly, at least in large forms having large legs. In proteus 
the regeneration may extend over a year and a half, and in necturus 
it takes more than a year to make a new limb, at least in animals in 
confinement. In the large form; amphiuma, that has extremely small 
legs, regeneration takes place much more rapidly than in a form like 
necturus having much larger legs (Fig. 39). 

In amphiuma the feet are not used by the animal as organs of 
locomotion, since they are too small and weak to support the heavy 
body. They can be moved by the animal in the same way that the 
feet are moved in other forms, and yet are useless for progression. 
It is said by Schreiber that the regeneration of the legs of Triton 
marmoratus is relatively very slight as compared with that of other 
forms. Fraisse also found in this form that an amputated leg did 
not grow again, only a deformed stump being produced. The tail 
also is said to regenerate to only a slight extent, but, so far as I know, 
there is nothing peculiar in the life of this form that makes it less 
liable to injury than other large urodeles.^ Weismann cites the case of 
proteus, which is said also to regenerate less well than do other forms. 
It lives in the caves of Carniola, where there are few other animals 
that could attack or injure it, and to this immunity is ascribed its lack 
of power of regeneration ; yet Goette states that he observed a regen- 
erating leg in this form, but that the process was not complete after 
a year and a half. In necturus also, which is not protected in any 
way, regeneration is equally slow. Frogs are unable to regenerate 
their limbs, although they are sometimes lost, but the larval tadpole 
can regenerate at least its hind legs. In the lizards the tail regen- 
erates, but at present we do not know of any connection between 
this condition and the liability of certain forms to injury. Turtles 
and snakes do not regenerate their tails. I do not know of any 
observations on crocodiles. 

In birds, the legs and wings are not supposed to have the power 
to regenerate,^ but in two forms ^ at least the beak has been found to 

^ I do not know whether this animal was kept long enough to make it certain that the 
legs do not regenerate. 

2 A statement to the contrary quoted in Darwin's Animals and Plants under Domestic 
cation is doubted by Darwin himself. 

* The stork and the fighting cocks. 

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REGENERATION AND UABIUTY TO INJURY lO/ 

possess remarkable powers of regeneration. There are a few very 
dubious observations in regard to the regeneration in man of super- 
fluous digits that had been cut off.^ 

These examples might be added to by others in the groups cited, 
and also by examples taken from the smaller groups of the animal 
kingdom, but those given will suffice, I think, to show that the power 
to regenerate is characteristic of entire groups rather than individual 
species. When exceptions occur, we do not find them to be forms 
that are obviously protected, but the lack of regeneration can rather 
be accounted for by some peculiarity in the structure of the animal. 
If this is borne in mind, as well as the fact that protected and unpro- 
tected parts of the same animal regenerate equally well, there is 
established, I think, a strong case in favor of the view that there is 
no necessary connection between regeneration and liability to injury. 
We may therefore leave this side of the question and turn our atten- 
tion to another consideration. 

It will be granted without argument that the power of replacement 
of lost parts is of use to the animal that possesses it, especially if the 
animal is liable to injury. Cases of usefulness of this sort are gener- 
ally spoken of as adaptations. The most remarkable fact in connec- 
tion with these adaptive responses is that they take place, in some 
cases at least, in parts of the body where they can never, or at most 
very rarely, have taken place before, and the regeneration is as per- 
fect as when parts liable to injury regenerate. Another important 
fact is that in some forms the regeneration is so slow that if the 
competition amongst the animals was very keen those with missing 
legs, or eyes, or tails, would certainly succumb ; yet, if protected, they 
do not fail to regenerate. If, therefore, the animal can exist through 
the long interval that must elapse before the lost part regenerates, 
we cannot assume that the presence of the part is of vital importance 
to the animal, and hence its power to regenerate could scarcely be 
described as the result of a " battle for existence," and without this 
principle " natural selection " is powerless to bring about its supposed 
result. 

It is extremely important to observe that some cases, at least, of 
regeneration are not adaptive. This is shown in the case where a new 
head regenerates at the posterior end of the old one in Plaiiaria 
lugubrisy or where a tail develops at the anterior end of a posterior 
piece of an earthworm, or when an antenna develops in place of an 
eye in several Crustacea. If we admit that these results are due to 
some inner laws of the organism, and have nothing to do with the rela- 
tion of the organism to its surroundings, may we not apply the same 
principle to other cases of regeneration in which the result is useful t 

^ See Darwin, loc cit. 

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I08 REGENERATION 

So firm a hold has the Darwinian doctrine of utility over the 
thoughts of those who have been trained in this school, that whenever 
it can be shown that a structure or a function is useful to an animal, 
it is without further question set down as the result of the death 
struggle for existence. A number of writers, being satisfied that the 
process of regeneration is useful to the animal, have forthwith sup- 
posed that, therefore^ it must have been acquired by natural selection. 
Weismann has been cited as an example, but he is by no means alone 
in maintaining this attitude. It would be entirely out of place to 
enter here into a discussion of the Darwinian theory, but it may be 
well worth while to consider it in connection with the problem of 
regeneration. 

We might consider the problem in each species that we find 
capable of regenerating ; or, if we find this too narrow a field for our 
imagination, we might consider the process of regeneration to have 
been "acquired by selection in the lower and simpler forms," and 
trace its subsequent progress as it decreased in the course of phylog- 
eny " in correspondence with the increase in complexity of organiza- 
tion," or with the decrease of exposure to injury. At the risk of 
adopting the narrower point of view I shall confine the discussion to 
the possibility of regeneration being acquired, or even augmented, 
through a process of natural selection in any particular species. 

The opportunity to regenerate can only occur if a part is removed 
by accident or otherwise. On the Darwinian theory we must suppose 
that of all the individuals of each generation that are injured, in 
exactly the same part of the bodyy only those have survived or have 
left more offspring that have regenerated. In order that selection may 
take place, it must be supposed that amongst these individuals injured 
in exactly the same regiony regeneration has been better in some forms 
than in others, and that this difference is, or may be, decisive in the 
competition of the forms with each other. The theory does not 
inquire into the origin of this difference between individuals, but 
rests on the assumption of individual differences in the power to 
regenerate, and assumes that these differences can be heaped up by 
the survival and inbreeding of the successful individuals ; i.e, it is 
assumed that, by this picking out or selection through competition in 
each generation of the individuals that regenerate best, the process 
will become more and more perfectly carried out in the descendants, 
until at last each part has acquired XhQ power of complete regeneration. 

There are so many assumptions in this argument, and so many 
possibilities that must be realized in order that the result shall follow, 
that, even if the assumptions were correct, one might still remain 
sceptical in regard to the possibilities ever becoming realized. If we 
examine somewhat more in detail the conditions necessary to bring 



cessary to t 

byGoOgk 



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REGENERATION AND LIABILITY TO INJURY 109 

about this supposed process, we shall find ample grounds for doubt, 
and even, I think, for denial that the results could ever have been 
brought about in this way. 

In the first place, the assumption that the regeneration of an 
organ can be accounted for as a result of the selection of those indi- 
vidual variations that are somewhat more perfect, rests on the 
ground that such variations occur, for the injury itself that acts as a 
stimulus is not supposed to have any direct influence on the result, 
t,e, for better or worse. All that natural selection pretends to do is 
to build up the complete power of regeneration by selecting the most 
successful results in the right direction. In the end this really goes 
back to the assumption that the tissue in itself has power to regen- 
erate more completely in some individuals than in others. It is just 
this difference, if it could be shown to exist, that is the scientific 
problem. But, even leaving this criticism to one side, since it is very 
generally admitted, it will be clear that in many cases most of the 
less complete stages of regeneration that are assumed to occur in the 
phyletic series could be, in each case, of very little use to the indi- 
vidual. It is only the completed organ that can be used ; hence the 
very basis of the argument falls to the ground. The building up of 
the complete regeneration by slowly acquired steps, that cannot be 
decisive in the battle for existence, is not a process that can be 
explained by the theory. 

There is another consideration that is equally important. It is 
assumed that those individuals that regenerate better than those that 
do not, survive, or at least have more descendants ; but it should not 
be overlooked that the individuals that are not injured (and they will 
belong to both of the above classes) are in even a l^etter position than 
are those that have been injured and have only incompletely regen- 
erated. The uninjured forms, even if they did not crowd out the 
regenerating ones, which they should do on the hypothesis, would 
still intercross with them, and in so doing bring back to the average 
the ability of the organism to regenerate. Here we touch upon a 
fatal objection to the theory of natural selection that Darwin himself 
came to recognize in the later editions of the Origin of Species, 
namely, that unless a considerable number of individuals in each gen~^ 
eration show the same variation, the result will be lost by the swamping \ 
effects of intercrossing. If this be granted, there is left very little j 
for selection to do except to weed out a few unsuccessful competitors, 
and if the same causes that gave origin to the new variation on a 
large scale should continue to act, it will by itself bring about the 
result, and it seems hardly necessary to call in another and question- 
able hypothesis. 

Finally, a further objection may be stated that in itself is fatal to 

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I lO REGENERA TION 

the theory. We find the process of regeneration taking place not 
only at a few vulnerable points, but in a vast number of regions, and 
in each case regenerating only the missing part. The leg of a sala- 
mander can regenerate from every level at which it may be cut off. 
The leg of a crab also regenerates at a large number of different 
levels, and apparently this holds for all the different appendages. If 
this result had been acquired through the action of natural selection, 
what a vast process of selection must have taken place in each species ! 
Moreover, since the regeneration may be complete at each level and 
in each appendage without regard to whether one region is more 
liable to injury than is another, we find in the actual facts themselves 
nothing to suggest or support such a point of view. 

If, leaving the adult organism, we examine the facts in regard to 
regeneration of the embryo, we find again insurmountable objections 
to the view that the process of regeneration can have been produced 
by natural selection. The development of whole embryos from each 
of the first two or first four blastomeres can scarcely be accounted for 
by a process of natural selection, and this is particularly evident in 
those cases in which the two blastomeres can only be separated by a 
difficult operation and by quite artificial means. If a whole embryo 
can develop from an isolated blastomere, or from a part of an embryo 
without the process having been acquired by natural selection, why 
apply the latter interpretation to the completing of the adult organism } 

Several writers on the subject of regeneration in connection with 
the process of autotomy (or the reflex throwing off of certain parts of 
the body) have, it seems to me, needlessly mixed up the question of 
the origin of this mechanism with the power of regeneration. If it 
should prove true that in most cases the part is thrown off at the 
region at which regeneration takes place to best advantage, it does 
not follow at all that regeneration takes place here better than else- 
where, because in this region a process of selection has most often 
occurred. The phenomenon of regeneration in the arm of the star- 
fish, that has been described on a previous page, shows how futile is 
an argument of this sort. If, on the other hand, the autotomy is 
supposed to have been acquired in that part of the body where regen- 
eration takes place to best advantage, then our problem is not con- 
cerned with the process of regeneration at all, but with the origin of 
autotomy. If the attempt is made to explain this result also as the 
outcome of the process of natural selection acting on individual vari- 
ations, many of the criticisms advanced in the preceding pages 
against the supposed action of this theory in the case of regeneration 
can also readily be applied to the case of autotomy. In Chapter 
VIII, in which the theories of autotomy are dealt with, this problem 
will be more fully discussed. 

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CHAPTER VI 

REGENERATION OF INTERNAL ORGANS. HYPERTROPHY. 

ATROPHY 

It is a more or less arbitrary distinction to speak of internal in 
contrast to external organs, since the latter contain internal parts ; but 
the distinction is, for our present purposes, a useful one, especially in 
regard to the question of regeneration and liability to injury. In this 
connection we shall find it particularly instructive to examine those 
cases of regeneration of internal organs that cannot be injured, under 
natural conditions, without the animal itself being destroyed. An 
illustration of this may be given. The liver, or the kidney, or the 
brain of a vertebrate can seldom be exposed to accidental injury with- 
out the entire animal being destroyed, although, of course, diseases 
of various kinds may injure these organs without destroying the ani- 
mal, but cases of the latter kind are not common. 

The experiments made by Ponfick (*9o) on the regeneration of the 
liver in dogs and in rabbits gave the most striking results. Ponfick 
found after removal of a fourth, or of a half, or even, in a few success- 
ful operations, of three-fourths of the liver, that, in the course of four 
or five weeks, the volume of the remaining part increased, and in the 
most extreme case, to three times that of the piece that had been 
left in the body. The first changes were found to have begun as 
early as thirty hours after the operation, when the liver cells had 
begun to divide. The maximum number of dividing cells was found 
about the seventh day, and then decreased from the twentieth to the 
twenty-fifth day, but cells were found dividing even on the thirtieth 
day. These dividing cells appeared everywhere throughout the liver, 
and were no more abundant at the cut-edges than elsewhere. There 
takes place, in consequence, an increase in the volume of the liver, 
rather than a replacement of the part that is removed. The increase 
takes place in the cells of the old part, the lobules swelling up to two, 
three, or even four times their former size. No new liver lobules 
seem to be formed. The old tubules of the liver also become larger, 
owing to an increase in the number of their cells. Since the change 
takes place in the old part, and is due to an increase in size of the 

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1 1 2 REGENERA TION 

lobules, tubes, etc., the process is spoken of as one of hypertrophy 
rather than of regeneration. 

Kretz found a case in which the entire parenchyma of the liver 
seemed to have been destroyed, presumably by a poison from some 
micro-organism, and later a regeneration of the tissue had taken 
place. If this conclusion is correct, it shows that sometimes an in- 
ternal organ may meet with an injury that does not directly destroy 
the rest of the body, and the animal may survive. 

The regeneration of the salivary gland of the rabbit described by 
Ribbert is another example of an internal organ that can seldom be 
injured, and yet can be replaced after artificial removal. Weismann 
('93) has recorded an experiment in which half of a lung of triton 
was cut off. After fourteen months the lung had not been restored 
in four individuals, and in one " it was doubtful whether a growth of 
the lung had not taken place, but even in this case it had not recov- 
ered its long, pointed form.*' 

The regeneration of the eye in triton was first made known by 
Bonnet. The right eye was partly cut out, and after two months it had 
completely regenerated. Blumenbach, in 1 784, removed the anterior 
part of the bulb of the eye of " Lacerta lactistris'' Six months later 
a smaller bulb was present. Phillipeaux ('80) found that if the eye 
of an aquatic salamander was not entirely removed, a new eye regener- 
ated ; but if the eye was completely extirpated a new eye did not 
appear. Colucci, in 1885, described the regeneration of the lens of 
the eye of triton from the edge of the optic cup. WolflF, later, inde- 
pendently, discovered the same fact, and it has been more recently 
confirmed by E. Miiller ('96), W. Kochs ('97), P. Rothig ('98), and 
Alfred Fischel ('98). The most important part of this discovery is 
that the new lens develops from the margin of the optic cup, and not 
from the outer ectoderm, as it does in the embryo. This result will 
be more fully discussed in a later chapter. It is highly probable in 
this case that the regeneration stands in no connection whatsoever 
with the liability of the eye to injury, for of the large number of 
salamanders that have been examined, none has been found with 
the eye mutilated. The position of the eye is such that it is well 
protected from external injury, and the tough cornea covering its 
outer surface would also further protect it from accidental injury. 
When we recall the high degree of structural complexity of the eye, 
its capacity to regenerate, if only a portion of the bulb is left, and its 
power to replace the lens if this is removed are certainly very remark- 
able facts. We find here, I think, an excellent refutation of the 
incorrectness of the general assumption of a connection between 
regeneration and liability to injury. Moreover, since there is no 
evidence whatsoever to show that the eyes in these animals are ever 

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REGENERATION OF INTERNAL ORGANS II3 

subject to diseases caused by bacteria, and much evidence to show that 
they are not so injured, we are still further confirmed in our general 
conclusion. 

It has been known for a long time that even in man the lens of 
the eye is sometimes regenerated after its removal. The regeneration 
has been supposed to take place from the old capsule of the lens, or 
possibly from a piece of the lens left after the operation ; but what- 
ever its origin, the fact of its regeneration in man, and in other mam- 
mals also, is a point of some interest in this connection. 

Podwyssozki (*86) found that regeneration may take place in the 
kidney of certain mammals, — best in the rat, more slowly in the rabbit. 
The restoration of the lost part takes place first by replacement of 
the epithelium. The old canals may then push out into the connec- 
tive tissue that accumulates in the new part, but there is no new for- 
mation of canals or of glomeruli. According to Podwyssozki the 
regeneration of the kidney is less complete than that of any other 
gland. Peipers has reinvestigated the subject, and his results agree 
in the main with those just given. He finds in addition that new 
canals may grow out from the old ones into the new part. 

Podwyssozki and Ribbert ('97) have found that the salivary gland 
has a remarkable power of regeneration. Ribbert removed a half 
(or even more than this) of the salivary gland of the rabbit. In the 
course of two or three weeks new material had developed over the 
cut-surface. In one case at least five-sixths of the gland had been 
taken out, and at the end of three weeks the gland had regenerated 
to its full size. Microscopic examination showed that the greater 
part of the gland was made up of new lobes, some of which were as 
large as, others smaller than, the normal lobes. The new part con- 
tained new tubes with terminal acini. These had arisen from the 
tubes of the old part. The connective tissue of the new part also 
came from that of the old. In this case a true process of regenera- 
tion takes place from the cut-surface ; in addition a certain amount of 
enlargement, or hypertrophy, also takes place in the old part. Rib- 
bert believes there is a connection between the process of hypertrophy 
and of regeneration of such a kind that the more active the one, the 
less active the other. 

Regenerative changes are known to occur in other internal organs 
besides these glandular ones. Broken bones are united, if brought in 
contact, by a process that involves a certain amount of regeneration. 
Although new bony tissue may be formed at the region of union, the 
bones of mammals and of birds do not seem able to complete them- 
selves, if a part is removed, except to a limited extent. While the 
broken bones of the leg or of the arm have the power of reuniting if 
held for some time in place, yet in nature this condition can seldom 

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1 1 4 KEGENERA TION 

be fulfilled, and the animal with a broken leg or wing will most prob- 
ably be killed. Nevertheless, since the bones have this power at 
whatever level they may be broken (but only if they are kept together 
artificially), the process can scarcely have been acquired through the 
liability of the parts to injury. We find here another instance of a 
useful process existing in animals, but one that could not have been 
acquired by exposure of the part to injury. It is probable that this 
same property is found in all the bones of the body, — in those that 
may occasionally be injured, and in those that are not. 

The muscles have also the power of regenerating, although few 
experiments have been made except in those forms in which the 
whole leg can regenerate, yet there are a few observations that show 
that even in mammals, in which the leg or the arm cannot regenerate 
as a whole, a certain amount of regeneration of the muscles them- 
selves may take place. 

It has been known for a long time that if a nerve is cut a new 
nerve grows out from the cut-end, and may extend to the organs sup- 
plied by that nerve. The process takes place more successfully if 
the peripheral part is left near the cut-end from which the new nerve 
grows. Whether this old part only serves to guide the new part to 
its proper destination, or whether it may also contribute something to 
the new nerve, as, for instance, cells for the new sheath, is not finally 
settled. The general opinion in regard to the origin of the new nerve 
fibres is that the central axis or fibril grows from the cut-end. That 
this power could have been acquired for each nerve as a result of its 
liability to injury is too improbable to discuss seriously. 

The central nervous system of the higher vertebrates seems to 
have very little power of regeneration, and although in some cases 
a wounded surface may be covered over and a small amount of con- 
nective tissue be formed, the development of new ganglion cells does 
not seem to occur. In other animals, as the earthworm, planarian, 
and even in the ascidian, as shown by Loeb, a new entire brain may 
develop after the removal of the old brain, or of that part of the 
body in which it is contained. 

This examination of the power of regeneration of internal organs 
in the vertebrates has shown that it is highly improbable that there 
can be any connection between their power of regeneration and their 
liability to injury. That the internal organs may be occasionally 
injured by bacteria, or by poisons made in the body, may be admitted, 
but that injuries from this source have been of sufficient frequency 
to establish a connection, if such were indeed possible, between their 
power of regeneration and their liability to injury from these causes 
is too improbable a view to give rise to much doubt. These results 
taken in connection with those discussed in the preceding chapter go 

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HYPER TROPHY 1 1 5 

far toward disproving the view that the power of regeneration has a 
connection with the liability of a part to injury. 

HYPERTROPHY 

The hypertrophy, or unusual enlargement, of organs has long 
attracted the attention of physiologists, and the extremely interesting 
observations and experiments that have been made in this connection 
have an important although an indirect bearing on the problem of 
regeneration. Ribbert, as has been pointed out, holds that the 
processes of hypertrophy and of regeneration stand in a sort of 
inverse relation to each other, but it is doubtful, I think, if any such 
general relation exists. Two kinds of hypertrophy are now generally 
distinguished : functional hypertrophy, which takes place when a 
part becomes enlarged through use ; and compensating hypertrophy, 
which takes place when one organ being removed another enlarges. 
The enlargement in the latter case may, of course, be brought about 
by the increased use of the parts that enlarge, but as this is not 
necessarily the case, the distinction between the two processes is a 
useful one. The causes of compensating hypertrophy are by no 
means simple, and several possibilities have been suggested to 
account for the enlargement. The best ascertained facts in con- 
nection with hypertrophy relate almost entirely to man and to a 
few other mammals.^ 

By hypertrophy is meant an increase of the substance of which 
an organ is composed. Swelling due to the imbibition of water or 
of blood-serum is not, in a technical sense, a process of hypertrophy. 
Virchow distinguishes two kinds of hypertrophy: (i) Hypertrophy 
in a narrower sense in which the enlargement is due to an increase 
in the size of the cells of which an organ is composed. This en- 
largement of the individual cells leads of course to an increase in 
the size of the whole organ. (2) Hyperplasy due to an increase 
in the number of cells of which an organ is composed, which also 
causes an enlargement of the whole organ if the cells retain the 
normal size. The division into functional and compensating hyper- 
trophy given above is a physiological distinction, and both of these 
processes might occur in Virchow's subdivisions. 

Giants may be looked upon as hypertrophied individuals, since all 
the organs of the body are larger than the normal. The enlargement 
is, in this case, not due to external influences, but to some peculiarity 

* The more generally accepted results are given in Virchow*s Cellular Pathology and 
in Ziegler's Pathological Anatomy, An excellent review of the subject down to 1895 
» given in a summary by Ludwig Aschoff in the Ergebnisse d, al^em. patholog. MorphoL 
und Physiologies 1895, " Regeneration und Hypertrophic," in which there are two hundred 
and eighteen references to the literature. 



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1 1 6 RE GENERA TION 

of the organism itself. Whether the size is due to more cells being 
present, as seems probable, or to the cells being larger, or to both, 
has not, so far as I know, been determined for man. In a mollusk, 
Crepidida forfiicata, in which large and small adult individuals occur, 
it has been shown by Conklin ('98) that the difference is due entirely 
to the larger number of cells in the larger individual. In this case 
external conditions, in so far as they retard the maximum possible 
growth of the individual, are responsible for the differences in size. 
The distinction is, in this case, rather between large normal indi- 
viduals and dwarfs, than between giants and normal or average 
individuals. 

The voluntary muscles of the body of man grow larger, and may 
be said to hypertrophy, as a result of doing certain kinds of work. 
The muscles of the hand and arm grow large through use, and 
become smaller again if not used ; but the muscles of the fingers of a 
musician do not hypertrophy, although the total amount of work done 
may be very large. It is only when muscular work is done against 
great resistance that enlargement of the muscles takes place. The 
factors that may bring about the enlargement will be discussed later. 

The kidneys seem to give the most satisfactory evidence of com- 
pensating hypertrophy. NothnageP states that it has been shown 
in man, in the rabbit, and in the dog, that when one kidney has been 
removed the other enlarges; and that this takes place both for young 
animals, in which the kidneys have not reached their full size, and in 
adult animals, in which the remaining kidney becomes larger than 
normal. In the adult the enlargement is due to hypertrophy, in 
Virchow*s sense, in the tubules and in the epithelium of the canals. 
In the young animal there is, in addition, a hyperplastic growth that 
leads to an increase in the number of glomeruli, etc. 

Experiments have shown that the same amount of urea is excreted 
by the animal after the removal of one kidney as before ; in fact, this 
is true immediately after the operation, before any increase in the 
size of the organ has taken place. This means that, under normal 
conditions, the kidneys do not perform their maximum of work. It 
is important to observe in this connection that the remaining kidney 
gets more blood than it would get if the other were present. Noth- 
nagel sums up the changes that take place in this way : First, the 
removal of one kidney ; second, an increase in the flow of blood in 
the remaining kidney ; third, an increase in the functional activity and 
excretion of this kidney ; fourth, along with the increase in the flow 
of blood, there is a necessary increase in the amount of food that is 

1 Nothnagel gives a review of the subject down to 1886 in an article entitled **Uher 
Anpassun^ und Aus^leichuttg bei pathologischen Zmtdnden. Zeitsch, f. klinische Medicin2* 
1886. Vols. X and XI. 



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HYPERTROPHY 1 1 7 

brought to the kidney in the blood ; fifth, this food is taken up in 
larger amount than before by the cells, which leads to an increase in 
the growth of the cells, which produces hypertrophy. The increase 
in size, looked at from this point of view, Nothnagel says, has nothing 
mysterious about it. The enlargement seems to be an adaptation ; but 
the enlargement does not take place because it is an adaptive process, 
but because it cannot be helped under the conditions that arise. We 
shall return again to Nothnagel's interpretation, when we come to 
consider other views. 

Experiments of the sort just described are most easily carried out 
on the paired organs of the body, such as the salivary glands, the 
tear glands, the mammae of the female, and the testes of the male. 
In regard to the latter two organs the evidence, especially in the case 
of the testes, is conflicting, but the recent experiments of Ribbert 
seem to give definite results. Nothnagel had found that after the re- 
moval of one testis there is no hypertrophy of the other. He pointed 
out that this result does not stand in contradiction to his hypothesis 
in regard to the kidneys, for the toss of one testis does not lead to 
a greater functional activity in the other. Each acts for itself alone. 
The result shows further, he adds, that the process of hypertrophy 
is not an adaptive one, but a physical or a physiological process. 
Ribbert on the contrary thinks that even Nothnagel's statistics give 
evidence of hypertrophy, and Ribbert's own experiments give un- 
mistakable evidence of a considerable enlargement of the remaining 
testis. In his experiments, young rabbits were used that were born 
of the same mother and in the same litter. One of the testes was 
removed from some of the individuals, and after some months the 
remaining testis was taken out and its weight compared with that 
of the control animal. In sixteen out of seventeen experiments there 
was found to be a noticeable increase in the single testis as compared 
with either testis of the control animal. The results show that in 
some cases the single testis weighs almost as much as the two to- 
gether of the control animal. It is important also to notice that 
in this case the enlargement has taken place in an organ that has not 
been active, as was the case with the kidney. 

Ribbert has also shown that hypertrophy takes place in the 
mammae of the rabbit after the removal of some of them. Five out of 
the eight mammae were removed in three cases, and seven out of the 
eight in two other cases from young rabbits about two months old. 
Ribbert found that if the operator is not careful to remove completely 
all the tissue of a mamma an active regenerative process takes place 
from the part that remains. After five and a half months the single 
remaining mamma of one animal measured six and one-half by three 
and four-fifths centimetres, and the corresponding one in the control 

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1 1 8 REGENERA TION 

animal five and three-fourths by three and one-half centimetres. The 
glandular tissue was also found less developed in the control animal. 

In another experiment the rabbit experimented upon bore young 
when it was six and a half months old. Soon after the birth of the 
young and before the mamma had been used the animal was killed 
and the single mamma that had been left was measured. It was 
much enlarged and projected more than the normal mammae. It 
measured nine by five centimetres. In a normal control animal ^ the 
corresponding mamma measured seven by five centimetres. The 
number of acini was in the proportion of sixteen in the animal oper- 
ated upon to ten in the normal. The results show a distinct com- 
pensating hypertrophy, due to a hyperplastic increase in the number 
of elements of the gland. 

A further example of compensating hypertrophy has been found 
after the removal of the spleen, when the lymphatic glands of other 
parts of the body become enlarged. There are also observations 
which go to show that after the removal of some of the lymphatic 
glands others undergo an enlargement. 

Ziegler^ has given a critical review of the various opinions and 
hypotheses that have been advanced to account for the process 
of hypertrophy. According to Cohnheim^ hypertrophy in bones, 
muscles, spleen, and glands is due to hyperaemia, i,e, increased blood 
supply. He thinks that neither mechanical nor chemical stimuli can 
cause directly new processes of growth. Recklinghausen* thinks 
that hypertrophy is not due to any extent to an increase in the food 
supply. Samuel^ explains hypertrophy as due to a removal of, or 
to a decrease in, the resistance to growth and also to the influence 
of the nerves. Klebs ^ thinks that three factors enter into the prob- 
lem, {a) inherited peculiarities, {p) overfeeding, {c) a removal of the 
controlling influences. Weigert believes that reparative processes 
are due to the removal of influences that prevent growth, and not 
to a direct stimulus. He thinks that a stimulus may start a func- 
tional act, but can never start a nutritive or a formative one. Good 
nourishment, for instance, may bring a tissue to a maximum develop- 
ment that is predetermined by innate peculiarities, but "idioplastic 
forces'* are not thereby increased. Pekelharing^ thinks that hyper- 
trophy is due to a disappearance of a resistance to growth, and also 
to a stimulus causing proliferation. 

We see from these various opinions how little is really known ; 

* Not, however, from the same litter. 

* InternaL Beitrhge zu wissensch. Medicin. Festschrift fur R, Virchow, Vol. II, 1891. 
' Vorlesungen iiber alUgemeine Pathologic, Vol. I, 1882. * Handbuch, 

* Handbuch d, allgem. Pathologic y 1879. « Allgemcine Pathologies Vol. II, 1889. 
' Uber Endothelwucherungen in Arterien. Bcitr, z, pathol. Anat,, Vol. VIII, 1 890. 



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HYPERTROPHY II9 

how little has been determined as yet by experiment as to the causes 
that bring about hypertrophy. Many of the views are more or less 
plausible in the absence of direct, experimental evidence, but it 
remains for the future to decide as to the correctness of all of them. 
They are valuable as suggestions, in so far as they show the different 
possibilities that must be taken into account 

Ziegler first advocated the view, in the first edition of his Lehrbitch, 
that hypertrophy is due to a lessening of the resistance to growth. 
He thinks that while hyperaemia and transudation may support the 
new growth, they are never the only cause of the formation of new 
tissue. While Virchow*s view that any injury to the body or to an 
organ excites proliferation finds support in the work of Strieker and 
Grawitz, yet the view has been combated by Cohnheim and by Wei- 
gert, and is no longer held by many pathologists. Ziegler points out 
that as a result of his own work, and that of his students, traumatic 
and chemical lesions are not followed at once by new growth of the 
tissue, but by degeneration of the tissue, and by changes in the cir- 
culation that lead to exudations. The new growth begins, at the 
earliest, eight hours after the operation, and generally only after 
twenty-four hours. Also after mechanical, chemical, or thermal 
injuries, a long interval elapses before phenomena of growth begin. 
The injury itself does not appear to produce the growth, but brings 
about those conditions that lead to cell-multiplication. Ziegler dis- 
cusses what is meant by the idea of a lessening of the resistance to 
growth. He himself does not mean by this that hypertrophy depends 
on changes in the physical conditions, because it is known that living 
phenomena are the outcome of chemical processes and it is,' therefore, 
d priori probable that the effect is brought about by chemical sub- 
stances in the fluids of the tissues. These substances affect func- 
tional actions, and may even bring about regenerative changes. This 
action of chemical substances on the formative activity of the cell is 
theoretically possible in either of two ways ; first, chemical substances 
of definite concentration are set free, or, second, chemical substances 
are present in the normal condition that prevent proliferation, but if 
their influence should be counteracted by other substances the condi- 
tions become favorable to growth. It is known in the case of certain 
unicellular organisms, that derive their nourishment from the surround- 
ing medium, that their increase in number may be retarded by the pres- 
ence of certain chemical substances. It is also known that certain 
organisms may themselves produce chemical substances that prevent 
their own multiplication. It is, therefore, at least conceivable that after 
a part has been injured a new substance may be produced that acts 
upon and destroys in the organ itself the substances there present that 
have prevented its further growth. The other interpretation is that 

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120 REGENERATION 

in the breaking down of the tissue of the organ a substance is pro- 
duced that excites the cells to proliferation. 

Kiebs suggested that the accumulation of the leucocytes at the 
wounded surface may act as a stimulus to growth, and that the chro- 
matin of their nuclei might be absorbed by the cells of the tissue, and 
combining with the nuclei of these cells bring about the new growth. 
But Ziegler points out that we now know that although the leucocytes 
are dissolved and absorbed over the wounded surface, no process of 
absorption, of the sort postulated by Klebs, takes place. Ziegler thinks 
that Nothnagel is wrong in supposing that an increase in the blood 
supply, bringing with it an increase in the nourishment, can account 
for the hypertrophy of the kidney. On the contrary he believes 
that the growth is the result of an increase in the function of the organ 
due to the increase of the chemical substance, urea, that is brought to 
the secreting cells. The muscles of the body also hypertrophy as a 
result of their activity and not as a result of the additional blood supply. 

In connection with these problems of hypertrophy it may be pointed 
out that, under certain conditions, blood vessels may enlarge and 
their walls become thickened. To cite a single example, Nothnagel 
found that if the femoral artery of the rabbit is tied, the blood vessels, 
that come off immediately above the ligature, and which have already, 
through their subdivisions, connections in the muscles with other 
branches of the same femoral artery (that come off below the liga- 
ture), grow larger after a time. This he believes to be due, in 
the first instance, to the increased speed of the blood in the ves- 
sels, and thereby the bringing to these arteries of an increased food 
supply. Other writers have given different interpretations. Ziegler 
himself believes that several factors may be capable of bringing about 
the result. He thinks it improbable that the increase in the food 
supply can alone be the cause, and thinks it much more probable that 
the increased work that the vessels must perform while carrying more 
blood will account for the enlargement. 

In connection with this discussion it may not be unprofitable to 
recall that in the regeneration of the lower animals we find simpler 
conditions in which proliferation of the cells takes place under cir- 
cumstances where many of the factors suggested in the above discus- 
sion are absent. In the first place we find that new growth may occur 
without any increase in the nourishment that is brought to the organ. 
Regeneration takes place in the entire absence of food, except so far 
as it may be stored up in the tissues. Even in a planarian that is 
starving and decreasing in size, proliferation of new cells will take 
place if a part is removed. In many of the lower forms there may 
be proportionately even a much greater proliferation than in the 
regeneration and hypertrophy in the mammalian organs. It is true 

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HYPERTROPHY 121 

that proliferation may be more active if the tissues are well fed, but 
this doe^ not show that the presence of food is a factor in the pro- 
liferation except so far as it keeps the proliferating cells in their best 
condition for growth. It is possible in many animals, more espe- 
cially in some of the lower forms, to force them to grow rapidly by 
supplying them with a large amount of food, and conversely by de- 
creasing the food to delay the growth. While this shows that the 
rate of growth is, within certain limits, a function of the amount of 
food, there may be also other factors that enter into the result, and 
in all cases there is an upper limit beyond which it is not possible to 
make the animal grow any larger. 

That the presence of certain substances may bring about the 
enlargement of a part must be admitted as probable. It has been 
shown, for instance, that after the removal of certain lymphatic 
glands other glands may become larger. This appears to be due to the 
greater activity of the gland, brought about probably by the presence 
of an increased amount of some specific substance. In this instance 
the result can scarcely be due to a decrease in the physical resistance 
to growth or to an increase in the blood flow, except so far as this 
is brought about by the increased activity. It is, of course, possible, 
even if it cannot be positively shown in the case of the lymphatic 
glands, that a substance in the blood causes the hypertrophy in cer- 
tain organs, while in others, as in the kidney, an increase in the blood 
flow may be also a factor in its hypertrophy. 

The view held by several pathologists, that hypertrophy and 
regeneration may be caused by the removal of a physical resistance 
to growth, cannot be looked upon as a very probable hypothesis. 
The experiments in grafting of hydra and lumbriculus show that 
regeneration may still take place when the physical resistance has 
been reestablished by grafting two pieces together. These results, 
which are more fully described in a later chapter, demonstrate that 
the growth is due to other influences. 

A comparison with the lower animals shows that proliferation 
takes place when all but three of the factors considered in connection 
with hypertrophy and regeneration in the higher forms have been 
eliminated. These are, first, the action of substances that act either 
directly or as counteracting some substance already present, as Zieg- 
ler suggests ; second, an innate tendency in the organism to complete 
itself; and, third, the use of the organ. It is impossible that the sec- 
ond factor enters into the problem of hypertrophy. In those cases 
in which regeneration takes place when a part of an organ is removed, 
as in the case of the liver, for example, the result may possibly also 
involve the second of the two factors, for the process is much like 
that of morphallaxis in the lower animals. ^^ , 

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122 REGENERATION 

If it be granted that the growth in a hypertrophied organ is 
brought about by some substance that increases the function of that 
organ, can we suppose the phenomenon of regeneration to be due 
to similar factors ? In other words, can we reduce both phenomena 
to the same principle ? The case is complicated by two facts that 
may be illustrated by concrete examples. If a piece is cut from the 
middle of the body of lumbriculus new cells are produced at both 
ends of the piece. If we suppose the proliferation is brought about 
by the accumulation of certain substances in the piece, we must still 
invoke other factors to account for the differentiation of the prolifer- 
ated material, since a head forms at one end and a tail at the other. 
All the hypothesis can do in itself is to account for a proliferation, 
not for the differentiation, and, both in the case of hypertrophy and in 
that of regeneration, it is the formation of new structures that we are 
chiefly concerned with, rather than the simple act of growth or of 
proliferation. If a piece of a hydra is cut off, the whole piece changes 
into the typical hydra form. Here there is no extensive process of 
proliferation, and the change is in the old part. It seems highly 
improbable that the production of substances in the piece could account 
for its change of form. These examples will suffice to show that in 
the process of regeneration it is very improbable that the change is 
brought about by special substances that may develop or be present 
in the part. We must suppose that during regeneration the forma- 
tion of the typical form is not the result of a stimulus originating in a 
chemical substance acting upon the living material, but due to changes 
brought about directly in the living part itself. We must conclude, 
therefore, that despite the apparently close connection between the 
phenomena of hypertrophy of uninjured organs and of regeneration, 
they may often involve different factors. 

If specific substances can bring about the hypertrophy of an organ, 
it is still not clear at present whether they do so by directly causing 
new growth, or whether their presence only stimulates the organ to 
greater activity and the activity of the organ is the cause of its 
growth. Since it must be supposed that in each organ a different 
specific substance brings about its activity and the consequent hyper- 
trophy. It seems more probable that the result is due to the activity 
itself rather than to a stimulus from the substance. This view is fur- 
ther supported by the fact that in the case of the muscles and of the 
blood vessels the hypertrophy is directly connected with their use. 
The greater use brings about a larger supply of blood, but the blood 
is only different in amount and not in its quality. It must be con- 
fessed that it is difficult to see how the use of a part could make its 
growth increase, for by use the tissues break down ; and we are not 
familiar with any other processes within the body that mal^e for the 

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ATROPHY 123 

building up of an organ in more than an inverse ratio to its breaking 
down. We are, however, familiar with phenomena of building up 
due to an increase in the food supply. It might appear from this to 
be more in accordance with what we find, to assume that the hyper- 
trophy is solely due to an increase in the food supply ; yet there are 
other facts known that show that an organ does not increase in size 
simply because it gets more blood, and that this occurs only when 
the organs have a greater functional activity. It is a safer conclu- 
sion, I think, at present to assume that both the activity of the 
organ and the increase in its supply of food acting together are 
factors in the result. On the other hand we are so much in the 
dark concerning the functioning and growth of organs that we can do 
little more, as the preceding pages show only too clearly, than specu- 
late in the vaguest sort of way as to what changes take place ; but 
since the processes seem to be within reach of experimental methods 
we can hope in the near future to learn more of how the pro- 
Cesses of hypertrophy are brought about. 

ATROPHY 

It would not be profitable to enter into a general discussion of 
the many cases of absorption, or of atrophy of parts of the organism, 
but a few examples may be given that have a general bearing on the 
topics discussed in this chapter. The more noticeable cases arise 
through disuse of an organ, as shown, for example, in the decrease 
in size of the muscles of man when they are not used. Since this 
may take place in a single group of disused muscles, when no such 
change occurs in other muscles of the same individual that are in 
use, the most obvious explanation is that the decrease is due directly 
to disuse. Since the blood that goes to all the parts is the same, 
the diminution cannot be ascribed to any special substance in the 
blood. The flow of blood into the disused muscle is less than when 
the muscle is used, and it might be supposed that atrophy is directly 
caused by the lessened nourishment that the muscle receives. There 
is also the possibility that the decrease is brought about by the 
accumulation of certain substances in the disused muscle itself, but 
since, in general, the breaking down of the muscle is most active 
when it is used, it seems improbable that the result can be due 
directly to this cause, unless indeed it could be shown that the sub- 
stances produced by a disused muscle are different from those in an 
active muscle. 

Lack of food, as is known, may cause organs to decrease, the fat 
first disappearing, and then in succession in vertebrates, the blood, 
the muscles, the glands, the bones, and the brain. Certain, poisons 

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124 REGENERATION 

may also affect definite organs and bring about a decrease in size, 
as when the thymus and mammae decrease from iodine poisoning, and 
certain extensor muscles after lead poisoning. Atrophy may also be 
brought about by pressure on a part, as when the feet or waist are 
compressed. In old age there may be a decrease in some of the 
organs, as in the bones, the testes and ovary, and even in the heart. 

Degenerative changes appear even in the young stages of some 
animals, as when the tail of the tadpole is absorbed and the arras of 
the pluteus of the sea-urchin are absorbed by the rest of the embryo. 

Especially interesting are the cases of absorption that take place 
when organs are transplanted to unusual situations in the body. 
Zahn transplanted a foetal femur to the kidney, where it continued to 
grow but was later absorbed. Fischer transplanted the leg of a bird's 
embryo to the comb of a cock, where it continued at first to grow, but 
after some months degenerated. The spleen, the kidney, and the 
testis have been transplanted, but they degenerate, and, in general, 
the larger the transplanted piece the more probable its degeneration. 
Small pieces of the skin have been transplanted from one individual 
to another, and it has been found that small pieces maintain them- 
selves better than large pieces. Ribbert's recent experiments in 
transplanting small pieces of different organs have been more success- 
ful than earlier experiments in which larger pieces were used. The first 
difficulty seems to be in establishing a blood supply to the new part, 
in order to nourish it. If the piece is quite small, it can absorb the 
substances, necessary to keep it alive, from the surrounding tissues, 
until the new blood supply has developed. 

In the lower animals grafting experiments have been more success- 
ful, because the parts can remain alive for a longer time. It is 
important to find, however, that even in these cases, a part grafted 
upon an abnormal region of the body is usually absorbed. Rand 
shows that if the tentacles of hydra become displaced, as sometimes 
happens when a piece containing the old tentacles regenerates (Fig. 
48, A-A^), the misplaced tentacles are absorbed ; and I can confirm this 
result. In hydra, the hollow tentacles are in direct communication 
with the central digestive tract, and a displaced tentacle seems to be 
in as good a position as a normal one, as far as its nourishment is 
concerned, yet it becomes absorbed. 

Rand also found, in other experiments, that when the anterior end 
of a hydra is grafted upon the wall of another hydra, the piece may 
maintain itself if it is large ; but it is slowly shifted toward the base 
of the hydra to which it is grafted, and then the two separate in this 
region. If the graft is small, it may be entirely absorbed into the 
wall of the animal to which it is attached. 

Marshall found that if the head of a hydra is partially^lit in two. 

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ATROPHY 125 

each half-head completes itself (as Trembley had already shown). The 
body then begins slowly to separate into two parts, beginning at the 
angle between the two heads, until finally the two parts completely sep- 
arate. King (19CXD) has repeated the experiment in a large number of 
cases with the same result It seemed that the division might be 
brought about by the weight of the halves causing the gradual sepa- 
ration of the body, but King has shown that this is not the case, for, 
when a double form remained hanging with its head down, it still 
divided into two parts (Fig. 47, A\ In this case, the weight of the two 
heads would cause the parts to come together rather than to separate, 
if gravity had any influence of the sort suggested. Marshall and 
King have also shown that if the posterior end of a hydra is split in 
two, the two parts do not continue to separate, but one of the two, if 
the pieces have been split some distance forward, may become con- 
stricted from the other, and, producing new tentacles at its apical 
end, become a new individual. 

I have carried out a series of experiments on planarians of a some- 
what similar nature. If the posterior end is split in two, the separa- 
tion extending into the anterior part of the worm (Fig. 44, C\ 
each half completes itself, but the halves do not separate unless they 
happen to tear themselves apart. If one of the pieces is cut off, not 
too near the region of union with the other half, a new posterior end, 
replacing that cut off, regenerates. If, however, the piece is cut off 
quite near the region or union of the halves, the piece that is left 
may be absorbed. 

The absorption of misplaced parts in the lower animals cannot be 
explained, I think, by any lack of nutrition, especially in the case of 
the tentacles of hydra. The result may be due either to the displaced 
part not receiving exactly those substances, perhaps food substances, 
that it gets in its normal position, or it may be due to some formative 
influence. At present we are not in a position to decide between 
these alternatives, and, while the former view seems more tangible, 
and the latter quite obscure, the latter may nevertheless be found 
to contain the true explanation. If the view that I have adopted in 
regard to the organization — namely, that it can be thought of as 
acting through a system of tensions peculiar to each kind of proto- 
plasm — is correct, it may be possible to account for the absorption of 
misplaced parts by some such principle as this. 

INCOMPLETE REGENERATION 

A somewhat unusual process of regeneration takes place when 
the jelly-fish, Gonio?tem7is vertens, is cut into pieces. As first shown 
by Hargitt, the cut-edges come together and fuse, and the. nieces 

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126 



REGENERATION 



assume the form of a bell, but the missing parts are not replaced.* I 
have worked on the same form and obtained substantially the same 
results. If the jelly-fish is cut in two, as indicated by the dotted line 
in Fig. 39^^, A and A\ each half closes in and assumes the form 
shown in B, B, Each new jelly-fish has only the two original radial 
canals that each half had when separated from the other. A faint 
line along the region of fusion of the pieces seems to represent a 
new radial canal, — it is not represented in the figures, — and each 




JbiG. 3^4. — A. Aboi.il view of Gonionemus vet tens, AK Side view of same. Dotted line in eacb 
indicates where jelly-fish was cut into halves. B, B. New Individual from a half. As seen 
from above and from the side. C, C^. New individuals from a \ piece. As seen from above 
and from the side. D. New individual from a piece less than J. It contained a part of one 
of the radial canals. A new proboscis with mouth regenerated in all pieces, but no new 
canals or tentacles. 

half-proboscis has completed itself. There are not formed any new 
tentacles, except perhaps one, or a few more, where the cut-edges 
meet. Thus there is actually very little regeneration, although the 
typical jelly-fish form is assumed by the half-piece. If a jelly-fish 
is cut into four pieces, each piece containing one of the radial 
canals, the pieces also assume the bell-like form, as shown in 
C, C. A new proboscis develops from the proximal end of the 
old radial canal, and since this end is often carried to one side 

1 Haeckel (1870) first showed, in another medusa, that pieces producMiew medusa. 

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ATROPHY 127 

during the closing in of the piece, the new proboscis lies not at the 
top of the sub-umbrella space, but, as seen in the figure, quite to one 
side. Pieces even smaller than these one-fourth jelly-fish will assume 
the bell-like form, especially if they contain a bit of the margin of the 
old bell and a part of one of the radial canals, as shown in Fig. 39^, Z>. 
Although I have kept these partial medusae for several weeks, and 
have fed them during this time, I have found that the missing organs 
do not come back. That these pieces do undergo a certain amount of 
regeneration is shown by the formation of a new proboscis, and, in 
certain cases, a new radial canal. Even the tentacles may be par- 
tially regenerated, as Hargitt has shown, — especially, as I have found, 
if the margin of the bell is cut off very near the base of the line of 
tentacles. Small knobs appear along the cut-edge, but the pieces die 
before regeneration goes very far. If, however, the margin is cut 
oflF in only one quadrant, new tentacles may be produced along the 
cut-edge. 



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CHAPTER VII 

PHYSIOLOGICAL REGENERATION. REGENERATION AND 
GROWTH. DOUBLE STRUCTURES 

During the normal life of an individual many of the tissues of the 
body are being continuously renewed, or replaced at definite periods. 
The replacement of a part may go on by a process of continuous 
growth, such as takes place in the skin and nails of man, or the re- 
placement may be abrupt, as when the feathers of a bird are moulted. 
It is the latter kind of process that is generally spoken of as physio- 
logical regeneration. In the same animal, however, certain organs 
may be continually worn away, and as slowly replaced, and other 
organs replaced only at regular intervals. 

Bizozzero has made the following classification of the tissues of 
man, on the basis of their power of physiological regeneration, 
(i) Tissues made up of cells that multiply throughout life, as the 
parenchyma cells of those glands that form secretions of a definite 
morphological nature; the tissues of the testes, marrow; lymph 
glands, ovaries; the epithelium of certain tubular glands of the 
digestive tract and of the uterus; and the wax glands. (2) Tis- 
sues that increase in the number of their cells till birth, and only 
for a short time afterward, as the parenchyma of glands with fluid 
secretions, the tissues of the liver, kidney, pancreas, thyroid, con- 
nective tissue, and cartilage. (3) Tissues in which multiplication of 
cells takes place only at an early embryonic stage, as striated muscles 
and nerve tissues. In these there is no physiological regeneration. 

There are many familiar cases of periodic loss of parts of the body. 
The hair of some mammals is shed in winter and in summer. Birds 
renew their feathers, as a rule, once a year. Snakes shed their skin 
from time to time. The antlers of deer are thrown off each year, 
and new ones formed accompanied by an increase in size and branch- 
ing of the antlers. In other cases similar changes may be associated 
with certain stages in the life of the animal. The milk-teeth of the 
mammals are lost at definite periods, and new teeth acquired.^ The 
larval exoskeleton of insects is thrown off at intervals, and after 

* In rodents, however, the incisors continue to grow throughout the life of the animal. 

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PHYSIOLOGICAL REGENERATION 1 29 

each moult the body increases in size ; but after the pupa stage is 
passed and the imago formed, there is no further moulting. In the 
Crustacea, on the other hand, the adult animals moult from time to 
time, and the upper limit of size is less well defined than in the insects. 
The larvae also pass through a series of moults. 

An interesting case of physiological regeneration has been de- 
scribed by Balbiani in a unicellular form, stentor. From time to time 
a new peristome appears along the side, moves forward and replaces 
the old peristome, that is absorbed as the new one comes into position. 
In other infusoria the peristome may be absorbed before encystment, 
and a new one appear when the animal emerges from the cyst. 
Schuberg states that when division takes place in bursaria the new 
peristome develops on the aboral piece in the same way as after 
encystment ; and Gruber observed that, when an aboral piece of an 
infusorian is cut off, a new peristome develops in the same way as 
after normal division of the animal. These observations indicate that 
the process of physiological regeneration may follow the same course 
and probably involves the same factors as the process of restorative 
regeneration. 

Tubularia absorbs its old hydranth-heads if placed in an aquarium, 
and regenerates new ones. It may even absorb the hydranth while 
growing in an aquarium, as Dalyell has shown, and presumably, there- 
fore, also under natural conditions. After each regeneration the new 
stalk behind the head increases in length. 

In plants, in which there is a continuous apical growth, new parts 
are being always added at the end of the stem, and old parts are con- 
tinually dying, as seen in palms. Most trees and shrubs in temperate 
climates lose their leaves once a year and produce new ones in the 
spring. Since the new leaves develop from the new shoots at the end 
of the stem and branches, the old ones can, only in a general way, be 
said to be renewed. 

That a very close relation exists between the process of physio- 
logical regeneration and restorative regeneration will be sufficiently 
evident from the preceding illustrations. We do not gain any insight 
into either of the processes, so far as I can see, by deriving the one 
from the other, for the process of restorative regeneration may be, in 
point of time, as old as that of physiological regeneration. This does 
not mean, of course, that the same factors may not be present in both 
cases. So similar are the two processes that several naturalists have 
attempted to show how the process of restorative regeneration has 
been derived from physiological regeneration. Barfiirth, recognizing 
the resemblance between the two processes, speaks of restorative 
regeneration as a modification of physiological regeneration, and 
Weismann also supports this point of view. He says : " Physiological 

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I30 REGENERATION 

and pathological regeneration obviously depend on the same causes, 
and often pass one into the other, so that no real line of demarca- 
tion can be irawn between them. We nevertheless find that in 
those animals in which the power of regeneration is extremely great 
physiologically, it is very slight pathologically. This proves that a 
slight power of pathological regeneration cannot possibly depend on 
a general regenerative force present within the organism, but rather 
that this power can be provided in those parts of the body which 
require a continual, periodic regeneration ; in other words, the regen- 
erative power of a part depends on adaptation." It is, I think, 
erroneous to state "that in those animals in which the power of 
regeneration is extremely great physiologically, it is very slight patho- 
logically.*' All that we are justified in concluding ifrom the evidence 
is that in some cases in which physiological regeneration takes place, 
as in the vertebrates, pathological (restorative) regeneration may not 
be well developed ; but even in these forms restorative regeneration 
is certainly present, and present especially in internal organs, as in 
the salivary gland, in the liver, and in the eye, which are little exposed 
to injury. How far physiological regeneration takes place in the 
tissues of the lower animals we do not know at present, except in a 
few cases, but far from supposing it to be absent, it may be as well 
developed as in higher forms. Weismann*s further conclusion, that 
because in some animals physiological regeneration is very great and 
restorative regeneration very slight, therefore the latter cannot "de- 
pend on a general regenerative force within the organism," is, I 
think, quite beside the mark. • In this connection we should not fail 
to notice a difference between these two regenerative processes that 
several writers have also called attention to, viz. that the power of 
cell-multiplication and the formation of new cells in each kind of 
tissue does not carry with it the power of restorative or even of phy- 
siological regeneration, in cases where several kinds of tissue make 
up an organ. For instance, if the leg of the mammal is cut off, the 
old cells may give rise to new ones, but the processes that would 
bring about the formation of the new leg are not present, or, rather, 
if present, cannot act. Thus, although the production of new cells 
from each of the different parts of the leg of a mammal may take 
place, yet the conditions are unfavorable to the subsequent formation 
of a new leg out of the proliferated cells. We should not infer that 
this power does not exist, but that under the conditions it cannot be 
carried out. The assumption that physiological regeneration is the 
forerunner of restorative regeneration, in the sense that historically 
the former preceded the latter and furnished the basis for the devel- 
opment of the latter, cannot be shown, I think to be even probable. 
This way of looking at the two processes puts them, I believe, in a 



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REGENERATION AND GROWTH I3I 

wrong relation to each other. We find both processes taking place 
in the simplest forms as in the unicellular protozoa, and present 
throughout the entire animal kingdom without any connection, 
excepting so far as they both depend on the general processes of 
growth characteristic of each organ and of each animal. This leads 
us to consider the general question of regeneration in its relation to 
the phenomena of growth. 

REGENERATION AND GROWTH 

It has been pointed out in several cases in which external factors 
influence the growth of a plant, or of an animal, that the same factors 
play a similar part in the regeneration. The action of gravity on the 
growth of plants has been long known, and that it is a factor in the 
regeneration of a piece of a plant has also been shown. The only 
animal in which gravity has been definitely shown to be an important 
factor during growth is antennularia, and it has been found that 
gravity is also a factor in the regeneration of the same form. Not 
only is this influence shown in the growth of the new part that has 
developed, but the same influence seems to be one of the factors that 
determines where the new growth takes place. This latter relation is 
known in only a few cases, for instance in plants, according to 
Vochting, and in antennularia, according to Loeb, so that, until 
further evidence is forthcoming, it is best not to extend this general- 
ization too far ; but it seems not impossible that it may be generally 
true. How an external factor may determine the location of new 
growth, as well as the subsequent development of the new part, we 
do not know at present. 

In regard to the internal factors that influence the growth and the 
regeneration of new parts, we are almost completely in the dark. In 
cases of hypertrophy of the kidney, etc., the evidence seems to show 
that a specific substance, urea, that is normally taken from the blood 
by this organ may, if present in more than average amounts, excite 
the cells to greater activity and to growth, but whether the urea itself 
does this directly, or only indirectly through the greater functional 
activity of the cells, has not, as we have seen, been ascertained. That 
growth is influenced by internal factors can be shown, at least in 
certain cases, even although we cannot refer to the definite chemical 
or physical factors in the process. Some experiments that I have 
made on the tails of fish show very clearly the action of an internal 
factor. If the tail of fundulus is cut off obliquely, as indicated by 
the line 2-2 in Fig. 40, A^ new material appears in a few days along the 
outer cut-edge. It appears to be at first equal in amount along the 
entire edge. As the material increases in width, it grows faster over 

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132 



REGENERATION 



that part of the edge that is nearer the base of the tail (Fig. 40, C\ 
This growth continues to go on faster on the lower side, until the 
rounded form of the tail is produced. If we make the oblique cut so 
that the part nearer the base of the tail is on the upper side, the result 
is the same in principle ; the upper part of the new material grows 
faster than any other part. If we make two oblique cuts on the same 








f A 





H I 

Fig. 40. — A. Tail of Fundulus heteroclUus. Lines indicate levels at which B and Cwere cut ofT. 
B. Regenerating from cross-cut. C. Regenerating from oblique cut. D, E. Regenerating 
from two oblique surfaces. G. Tail of stenopus. H, L Tail of last cut ofT squarely and 

obliquely. 

tail, as shown in Fig. 40, Z>, or as in E^ the new part grows 
faster in each case on that part of the cut-edge that lies nearer the 
base of the tail. These results may be supposed to be due to the better 
nourishment of the new tissues nearer the base of the tail ; but it is 
not difficult to show that the difference in the rate of growth over 
different parts of the cut-edge is not due to this factor. If, for 

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REGENERATION AND GROWTH 133 

example, we cut off the tail of one fish squarely near the outer end, 
as shown in Fig. 40, F, i-i, and the tail of a second near the base of the 
tail, as shown in Fig. 40, F^ 2-2, and of a third by an oblique cut that 
corresponds to a cut extending from the upper side of the cut-edge of 
the tail of the first fish to the lower cut-edge of the tail of the second 
fish, as shown in Fig. 40, /% we find that the rate of growth over the 
first and second tails is about the same as that of the lower side 
of the third tail. In other words, the maximum rate of growth that 
is possible for the entire oblique edge is carried out only near the 
lower edge, and the growth of the rest of the new material is held in 
check. By means of another experiment a similar phenomenon can 
be shown. If the bifurcated tail of a young scup {Stenopus chrysops) 
is cut off by a cross-cut (Fig. 40, Gy i-i), it will be found that at first 
the new material is produced at an equal rate along the entire cut- 
edge; but it soon begins to grow faster at two points, one above and 
the other below, so that the characteristic swallow-tail is formed at a 
very early stage (Fig. 40, H) and before the new material has grown 
out to the level of the notch of the old tail. If the tail of another 
individual is cut off by an oblique cut (Fig. 40, G, 2-2), we find, as 
shown in Fig, 40, /, that at two points the new tail grows faster, but 
the lower lobe faster than the upper one. 

These results show very clearly that in some way the development 
of the typical form of the tail influences the rate of growth at different 
points. The more rapid growth takes place in those regions at which 
the lobes of the tail are developing. In other words, although the 
physiological conditions would seem to admit of the maximum rate of 
growth over the entire cut-edge, this only takes place in those parts 
that give the new tail its characteristic form. The growth in other 
regions is held in check. The same explanation applies to the more 
rapid growth at that part of an oblique cut that is nearest the base 
of the tail, for by this means the tail more nearly assumes its typical 
form. 

These results demonstrate some sort of a formative influence in 
the new part. We can refer this factor at present only to some 
structural feature that regulates the rate of growth. We find here 
one of the fundamental phenomena behind which we cannot hope to 
go at present, although it may not be beyond our reach to determine 
in what way this influence is carried out in the different parts. This 
topic will be more fully considered in a later chapter. 

Another illustration may be given from certain experiments in 
the regeneration of Planaria lugtibris. If the posterior end is cut 
off just in front of the genital pore, as indicated in Fig. 41, new 
material develops at the anterior cut-edge, and in a few days a new 
head is formed out of this new material. A new pharynx^ppeaijs 

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134 



REGENERATION 



in the new tissue immediately in front of the old part. It lies, 
therefore, just behind the new head. The proportions of the new 
worm are at this time very different from those of a typical worm, 
since the head is much too near to the new pharynx and to the old 
genital pore. New material is now produced in the region behind 
the head and in front of the pharynx, so that the head is carried 
further forward until the new worm has fully assumed the character- 
istic proportions. As the new head is formed the old part loses its 
material, so that it becomes flatter and narrower, and if the worm is 
not fed the old part may lose also something of its former length. 
If the worm is fed, however, as soon as the pharynx develops the 
old part loses less and the new part grows forward more rapidly. 





(^ 








Fig, 41. — Posterior end of Planaria lugubris, cut off between pharyngeal and genital pores. 
Figure to left shows the piece after removal. The four figures to the right show the regenera- 
tion of the same piece, drawn to scale. As soon as the new pharynx had developed, the 
worm was fed. The experiment extended from November 17 to January 8. 

The most striking phenomenon in the growth of the new worm is 
the formation of new material in the region behind the head. The 
result of this growth is to carry the head forward and produce the 
characteristic form of the animal. This change is all the more in- 
teresting since the growth does not take place at a free end, but in 
the middle of the new material. It is only by the formation of new 
material in this region that the head is carried to its proportionate dis- 
tance from the pharynx. It appears that in some way the growth is 
regulated by influences that determine the form of the new organism. 
Another experiment on the same animal gives also a somewhat 
similar result. If a worm is cut in two obliquely (Fig. 21, E) and 
the regeneration of the posterior piece is followed, it is found that 
the new material appears at first evenly along the entire^ut-surface. 

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DOUBLE STRUCTURES 135 

It then begins to grow faster on one side (Fig. 21, b\ and a head 
appears in this region with its axis at right angles to the cut-edge. 
As the head grows larger the growth is more rapid on one side, and 
as a result the head is slowly turned forward (Fig. 21, b). This 
more rapid growth on one side brings the new head finally into its 
typical position with respect to the rest of the piece. The end result 
of these changes is to produce a new worm having a typical form. 
If the oblique cut is made behind the old pharynx, as in Fig. 22, A, 
the new pharynx that appears in the new material along the cut-edge 
lies obliquely at first, indicating that the new median line is very 
early laid down in the new part, and connects the middle line of the 
old part with the middle of the new head. As the region behind the 
new head grows larger and broader the pharynx comes to lie more 
and more in an antero-posterior direction, and finally, when the new 
part is as broad as the old,^ the pharynx lies in the middle line of 
a symmetrical worm. 

These results show that the new growth may even take place 
more rapidly on one side of the structural median line than on the 
other, and on that side that must become longer in order to produce 
the symmetrical form of the worm. Here also we find that a for- 
mative influence of some sort is at work that regulates the different 
regions of growth in such a way that a typical structure is produced. 
The more rapid growth on one side is, however, in this case clearly 
connected with the relatively smaller development of the organs on 
that side, and perhaps this same principle may explain all other 
cases. If so the phenomenon appears much less mysterious than 
it does when the growth is referred to an unknown regulative factor. 

DOUBLE STRUCTURES 

A Structure that is single in the normal animal may become 
double after regeneration, and in some cases the special conditions 
that lead to the doubling have been determined. Trembley showed 
that if the head of hydra is split lengthwise into two parts, 
each part may complete itself and a two-headed form is produced. 
If the posterior end of a hydra is split, an animal with two feet is 
made. It is true that the two-headed forms may subsequently sepa- 
rate after several weeks into two individuals, and even the form 
with two feet may lose one of them by constriction, as Marshall and 
King have shown. Driesch has produced a tubularian hydroid with 
two heads by splitting the stem partially into two pieces. Each head 
is perfect in all respects, and although each has fewer tentacles than 

1 If the young worm is fed the new part becomes almost as broad as the old piece, but 
if the worm is not fed the old part decreases in breadth and the new part does not grow as 
broad as in the former case. 



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136 



REGENERATION 



the head that regenerates from an undivided stem, yet the number of 
tentacles on each head is more than half the average number. This 
is connected apparently with the fact that the circumference of each 
half is greater than half the circumference of the original stem. 
Planarians with double tails, produced by partial splitting, have been 
described by Duges and by Faraday, and it has also been shown 
that by partial splitting of the anterior end of the worm two heads 
can be produced. Van Duyne, Randolph, and Bardeen and I have 
obtained the same result. Each half completes itself on the cut-side 
and produces a symmetrical anterior end. If one of the heads is cut 
off, it will be again regenerated. If the heads are united very near to 
the trunk, as in Fig. 42, A, they may never grow to the full size of the 





B 



Fig. ^2,— Planaria lugubris. A, Two heads produced after operation similar to that in Fig. 24. 
Each head about half size. B, Worm split in half through level of pharynx. New half-worms 
larger than half of normal worm. 

original head, as I have found; but if the pieces have been split poste- 
riorly, so that each head has a long anterior end, then each one may 
become nearly as large as the original head (Fig. 42, B\ We see 
in these cases the influence of the region of union on the growth of 
the new part. If the new part is near the region of attachment, the 
smaller size of the latter restrains the growth of the new head; but 
if the region of union is farther distant, the head may grow more 
nearly to its full size despite the influence of the region of union. 
King has found in the starfish that if the arm is split lengthwise, each 
half may complete itself laterally and a forked arm result. An addi- 
tional entire arm may be formed by splitting the disk partially in two 
between two arms. If the cut-edges do not reunite a new arm will 
grow out from each cut-surface (Fig. 38, E), In this case the de- 



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DOUBLE STRUCTURES 137 

velopment of the new arm cannot be accounted for on the assump- 
tion that the typical form completes itself, since a sixth arm cannot 
be supposed to be a typical structure in the starfish. The result must 
depend on other factors, such as the presence of an open surface in a 
region where the cells have the power of making new arms. 

Barfurth has been able to produce a double tail in the tadpole by 
the following method: A hot needle is thrust into one side of the 
tail, so that the notochord and the nervous system are injured. The 
tail is then cut off just posterior to the region injured by the needle. 
A new tail grows out from the cut-end, and also in some cases an- 
other tail grows out at the side where the notochord was injured by 
the needle. The injury to the notochord and the removal of tissue 
immediately about it leads to a proliferation of cells, around which 
other tissues are added and the new tail produced. 

Lizards with double tails have often been described,^ and it now 
appears that all these cases are due to injuries to the normal tail. 
Tornier has succeeded, experimentally, in producing double and 
even triple tails. If the end of the tail is broken off, and the tail 
is then injured near the end, two tails may regenerate, one from 
the broken end and one from the region of injury (Fig. 43). Under 
natural conditions this might occur if the tail were partially bitten off 
and the end of the tail lost at the same time. A regenerated tail may 
produce another tail if it is wounded. A three-tailed lizard may be 
made by cutting off the tail and then making two injuries proximal 
to the broken end. Two of the new tails may be included in the 
same outer covering if they arise near together, as shown in Fig. 
43, B. Lizards with two or three tails may be produced in another 
way. If the tail is cut off very obliquely, so that two or three verte- 
brae are injured, there arises from each wounded vertebra a cartilagi- 
nous tube that forms the axis of a new tail. Tornier thinks that 
the regeneration is the result of overnourishment of the region where 
the injury has been made, but this does not seem in itself a sufficient 
explanation. Tornier has also been able to produce, experimentally, 
double limbs in Triton cristatiis in the following way : The limb is 
cut off near the body, and, after the cut-end has formed new tissue, 
a thread is tied over the end in such a way that it is divided into two 
parts. As the new material begins to bulge outward it is separated into 
halves by the constricting thread, and each part produces a separate 
leg (Fig. 43, D\ The soles of the two feet in the individual repre- 
sented in Fig, 43, Z>, are turned toward each other. The femur is 
bifid at its outer end, and to each end the lower part of one leg is 
attached. The bones in this part are fused together at the knee, so 
that only the foot portions can be separately moved. 

^ See Fraisse for literature. 

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138 



REGENERA TION 



The same method used to produce double tails in the lizard can 
also be used to produce double legs. The femur is broken in the 
vicinit)' of the hip-joint, and the soft parts are cut into over the break. 
Then, or better somewhat later, the leg is amputated below the 




Fig. 43. — After Toraier. A. Lacerta agilis. Produced by partly breaking off old tail. New tail 
arises at place of breaking. Old tail also remains. B. Three-tailed form — two tails being 
united in a common covering. Old tail had been cut off (it regenerated the lower branch 
from cut-end) and two proximal vertebrae that had been injured. C. Additional limb of 
Triton cristatus produced by wounding femur. D. Double foot of Triton cristatus produced 
by tying thread over regenerating stump. E, Foot of Triton cristatus. Dotted lines indicat- 
ing how foot was cut off. F, Regeneration of same. G. Another way of cutting off foot. 
H. Result of last operation. 

broken part. A new limb regenerates from the cut-end, and at the 
same time another limb grows out from the broken femur (Fig. 43, C). 
The same result is reached if the femur has a slit cut into it in the 
region of the hip-joint, so that it is much injured. Later the leg is 
cut off below the place of injury. A double leg is the result. 



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DOUBLE STRUCTURES 1 39 

Feet with supernumerary digits can also be produced by artificial 
wounds. If the first and second and then the fourth and fifth toes 
are cut off, as indicated by the lines in Fig. 43, E^ so that a part of 
the tarsus and a part of the tibia and fibula are cut away (the 
third finger being left attached to the remaining middle portion), more 
toes grow out from the wounded surface than were removed, as shown 
in Fig. 43, F. A similar result may be obtained in another way. If 
the first and second toes are cut off by an oblique cut (Fig. 43, G)^ 
and then after the wound has healed the third, fourth, and fifth toes 
are also cut off by another oblique cut (a part of the tarsus being 
removed each time), more toes are regenerated than were cut off ^ 
(Fig. 43. H). 

Tornier suggests that the double feet that are sometimes formed in 
embryos — even in the mammalia — have resulted from a fold of the 
amnion constricting the middle of the beginning of the young leg, in 
the same way as is brought about artificially by tying a string over 
the growing end of the regenerating leg of triton. 

In many of these cases, in which the double structure is the result 
of splitting the part in the middle line, the completion of the new 
part is exactly the same as though the parts had been entirely sepa- 
rated. The only special problem that we meet with in these instances 
is that this doubling is possible while the piece remains a part of the 
rest of the organism. This shows that there is a great deal of inde- 
pendence in the different parts of the body in regard to their regen- 
erative power, and that local conditions may often determine the 
formation of double structures. 

It has been shown during the last decade that double embryos may 
be produced artificially by incomplete separation of the first two 
blastomeres. Driesch, Loeb, and others have demonstrated that if the 
first two cells of the egg of the sea-urchin be incompletely separated, 
each may produce a single embryo and the two remain sticking to- 
gether. Wilson has shown in amphioxus that the same result occurs 
if the first two cells are partially separated by shaking. Schultze has 
shown in the frog that if at the two-cell stage the egg is held in an 
inverted position, Le, with the white hemisphere turned upwards, each 
blastomere gives rise to a whole embryo — the two embryos being 
united, sometimes in one way, sometimes in another, as shown in Fig. 
63. In this case it appears that the results are due to a rotation of 
the contents of each blastomere, so that like parts of the two blasto- 
meres become separated. In the egg of the sea-urchin, and of am- 
phioxus, gravity does not have a similar action on the ^^g, but the 
results seem to be due to a mechanical separation of the blastomeres. 
These cases of double structures, produced by the segmenting egg, 

1 In the figure one double or forked toe is present. 

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I40 



REGENERATION 



appear to belong to the same category as those described above for 
adult forms — especially in those cases where pieces regenerate by 
morphallaxis. 

In connection with the production of double structures there 
should be mentioned a peculiar method of formation of new heads, 
first discovered by Van Duyne in a planarian. He found that if the 







Fig. 44. — A. Planaria iugubris, cut in two as far forward as region between eyes, regenerating 
half-heads. B. Same cut in two at one side of middle line. Smaller piece produced a new 
head. C. Planaria maculata, split in two. It produced two heads in angle. D, Another, 
that produced a single head in angle. 

animal is cut in two in the middle line, the halves being left united 
only at the head-end, as shown in Fig. 44, D, C, there may appear one 
or two new heads in the angle between the halves. I have repeated 
this experiment with the same result, and have found that it may also 
occur when only a piece is partially split from the side of the body, 
as shown in Fig. 44, B. In Van Duyne's experiment the two new 



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DOUBLE STRUCTURES I4I 

heads do not appear unless the cut extends far forward, but if the 
division extends into the region between the two eyes there may be 
formed, as I have found, a single eye on each side that makes a pair 
with the old eye of that side (Fig. 44, A), It is evident in this case 
that each head has completed itself on the cut-side, the completion 
including the eye and the side of the head also with its "ear-lobe." 
The result, in this case, is the same as though the pieces had been 
completely cut in two. If the cut does not extend quite so far for- 
ward there are usually formed one or two heads near the angle, each 
with a pair of eyes and a pair of ear-lobes (Fig. 44, C\ Sometimes 
a single head develops in the angle itself (Fig. 44, D\ and it is diffi- 
cult to tell whether it belongs to one or to the other side, or whether 
it is common to both sides. Van Duyne spoke of the double and 
single head of the latter kind which he obtained as heteromorphic 
structures in Loeb's use of the term. According to this definition, 
heteromorphosis is the replacement of an organ by one that is morpho- 
logically and physiologically unlike the original one, but this statement 
has been made to cover a number of different phenomena. The 
examples of heteromorphosis that Loeb gives by way of illustration of 
the phenomenon are : the production of a hydranth on the aboral end 
of tubularia, and the formation of roots in place of a stem in anten- 
nularia, etc. The formation of the heads in the angle in planarians 
does not appear to me to belong in this category. It seems rather 
that the phenomenon is of the same sort as the formation of a new 
head at the side of a longitudinal piece, and if so the new heads in 
the angle are, therefore, in their proper structural position for new 
heads belonging to the posterior halves. Even if it should prove 
true that a single head may develop exactly in the angle itself, and 
belong to both sides, it can be interpreted by an extension of the same 
principle.^ The position of this median head turned backward sug- 
gests an obvious comparison with the production of the heteromor- 
phic head in Planaria lugubris^ but a closer examination will show, 
I think, that the two cases are different. The heteromorphic head 
is produced only when the head is cut off close behind the eyes. If 
cut off slightly behind this region, a posterior end is generally 
formed. But in the worms split lengthwise the head in the angle 
may be formed at a level much farther posteriorly than the eyes. If 
the split extends into the head, then the eyes that develop are the sup- 
plements of those of the old part. Our analysis leads, therefore, to 
the conclusion that the heads, or parts of heads, in the split worms 
are not heteromorphic structures but supplementary heads. 

1 A parallel case is found when a piece partially split in two at the anterior end (Fig. 24) 
produces one or two heads on each half, according to the extent of fusion of the new mate- 
rial that goes to form the new head or heads. 



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CHAPTER VIII 

SELF-DIVISION AND REGENERATION. BUDDING AND REGEN- 
ERATION. AUTOTOMY. THEORY OF AUTOTOMY 

Self-division, as a means of propagation, is of widespread occur- 
rence in the animal kingdom. In some cases the animal simply 
breaks into pieces and subsequently regeneration takes place in the 
same way as when the animal is cut into pieces by artificial means. 
In other cases the parts are gradually separated, and during this 
time new parts are formed by a process resembling that of regenera- 
tion after separation. A few zoologists have tried to show how the 
process cf regeneration before separation has been derived from 
regeneration following self-division. It is our purpose to examine 
here the evidence in favor of this hypothesis. 

A study of the forms that propagate by means of self-division 
shows that the process is present in many groups of the animal 
kingdom. In the unicellular forms this method is universally present ; 
and in the multicellular forms the division of the individual cells is 
looked upon as a process similar to the method of propagation in the 
protozoa. The sponges do not multiply by self-division. In the 
coelenterates, on the other hand, we find this mode of propagation 
present in most forms. Hydra appears rarely, if at all, to divide by 
a cross-division, and, although one or two cases of longitudinal 
division have been described, it is not improbable that they have 
been started by the accidental splitting of the oral end. The hydro- 
medusae, Stotnobrachititn mirabile^ Phialidiiim variabiles Gastroblasta 
Raffcelei, are known to increase by division.^ Several actinians and 
many corals divide longitudinally, while the scyphistoma of the 
scyphomedusae produce free-swimming ephyras by cross-divisions 
of the fixed strobila stage. The ctenophors do not divide. 

It is known that several fresh-water planarians propagate by 
division, the tail-end breaking off in the region behind the old 
pharynx. In one form,^ and possibly in others, regeneration may 
begin before the separation takes place. Many of the rhabdocoe- 
lous planarians increase by cross-division — the separation taking 
place more nearly in the middle of the body. In these forms the 

1 See Lang (»88). » See Zacharias ('86). 

142 

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SELF^DI VISION AND REGENERATION 1 43 

parts develop new organs more or less completely before they sepa- 
rate. In the trematodes self-division does not take place. The 
division of the body of the tapeworm into proglottids may represent 
a process of self -division, but the proglottids do not regenerate after 
separation. 

The nemertians break up readily into pieces, if roughly treated 
or if the conditions of life are unfavorable, but this can scarcely be 
spoken of as a process of voluntary self-division. Regeneration 
takes place in some species, but imperfectly or not at all in others. 

In the group of annelids we find many cases of self-division, 
especially in marine polychsetes and in fresh-water oligochaetes. One 
of the most interesting forms, belonging to the first group, is the palolo 
worm in which the swimming headless form, that is set free by divi- 
sion, serves to distribute the sexual products. Subsequently it appears 
that the piece dies without regenerating a new head. If we examine 
more in detail some of the cases of self-division in annelids, we find 
the following interesting facts. In nereis the posterior region of the 
body undergoes great changes of structure, the new worm being 
known under a different name, viz. heteronereis. In this part of 
the worm, eggs (or sperm) are produced, but it does not separate 
from the anterior end as a distinct individual. In the family of 
scyllids the changes that take place in the posterior or sexual end of 
the body are often accompanied by non-sexual modes of fission. 
In some species the changes that take place are like those in 
nereis, and no separation occurs ; in other species the sexual region 
becomes separated from the anterior or non-sexual regions. In 
scyllis a new head develops, after separation^ on the sexual or pos- 
terior piece. A new tail is also regenerated by the non-sexual or 
anterior piece, and as many new segments are formed as are lost. 
The new posterior region may again produce sexual cells, and again 
separate. In autolytus a new head develops on the posterior piece 
before it separates. A region of proliferation is also found at the 
posterior end of the anterior part. In some species new individuals 
develop in this zone of proliferation, and a chain of as many as six- 
teen worms may be present before the one first formed drops off. A 
still more complicated process is found in myriana. The region just 
in front of the anus elongates, and gives rise to a large number of 
segments. These form a new individual with the head at the ante- 
rior end. Then another series cf segments is proliferated at the 
posterior end of the old, or anterior worm, and just in front of the 
first-formed individual. This region also makes a new individual. 
The process continuing, a chain of individuals is produced, with the 
oldest individual at the posterior end and the youngest at the ante- 
rior end of the series. Each individual grows larger, and ijroduces 

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144 REGENERATION 

more segments at its posterior end. Reproductive organs appear in 
each individual, and when the germ-cells are mature the chain 
breaks up. 

None of the earthworms propagate by self-division, although occa- 
sionally, under unfavorable conditions, pieces may pinch off at the 
posterior end.^ Lumbriculus, on the other hand, propagates by self- 
division, although it has been disputed whether the division takes 
place without the intervention of an external injury or disturbance of 
some sort, or whether the division may take place entirely from inter- 
nal causes, that is, spontaneously. Von Wagner has shown that at 
certain seasons lumbriculus breaks up much more readily than at 
other times, which may only mean that it is more sensitive to stimuli 
at one time than at another. 

The pieces into which lumbriculus breaks up regenerate after 
separation. In another form, Ctenodrilus monostyloSy division takes 
place first in the middle of the body behind a cross-septum. Each 
half may again divide in the same way, and the same process may be 
repeated again and again until some of the pieces are reduced to a 
single segment. A new anterior and posterior end may then develop 
on each piece. In Ctenodrilus pardalis each segment of the middle 
region of the body constricts from the one in front and from the one 
behind, and each produces a new head at its anterior end and an anal 
opening at its posterior end. The worm then breaks up into a num- 
ber of separate worms. In this series, self-division of the individual 
is not associated with the development of sexual forms, but seems to 
be a purely non-sexual method of reproduction. In the leeches self- 
division does not occur, and no cases are known in the mollusks. 

In the echinoderms several forms reproduce by voluntary self-di- 
vision. In the brittle-stars some forms divide by the disk separating 
into two parts, one having two and the other three of the old arms. 
Each piece of the disk then regenerates the missing part of the disk 
as well as the additional arms. In the starfishes the arms may be 
thrown off if injured, and, while in certain forms the lost arm does 
not regenerate a new disk, yet, according to several writers, it 
may in other species regenerate a new animal. Dalyell observed a 
process of self-division in a holothurian, each part producing a new 
individual, and more recent observers have confirmed this discovery. 

No cases of self-division are known in the groups of myriapods, 
insects, crustaceans, spiders, polyzoans, brachiopods, enteropneusta, 
or vertebrates. 

Before discussing the general problems connected with the pre- 
ceding cases, I should like to point out that it is certainly a striking 
fact that in all, or nearly all, of these cases of self -division, the sepa- 

1 See Ilescheler ('97). 

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SELF-DIVISION AND REGENERATION 145 

ration takes place in the shortest axis, without regard to the structure 
of the animal. A law similar to that enunciated in connection with 
the division of the cell seems to hold for the organism as a whole : 
namely, division takes place, as a rule, in the shortest diameter of the 
form. The protozoa are, in a sense, excluded, since being unicellular 
forms they come under the rule for the division of the cell. In the 
coelenterates we find the actinians and corals, that have short, cylin- 
drical bodies, dividing from the oral to the aboral end, while the longer 
scyphistoma divides transversely. The flat, bell-shaped medusa, gas- 
troblasta, divides in an oral-aboral plane. The flat-worms and an- 
nelids divide transversely, and, therefore, in the plane of least resist- 
ance. The most important illustrations of this principle are furnished 
by the echinoderms. Those brittle-stars that divide through the disk 
do so in the shortest direction, that is, from the oral to the aboral side, 
whilst the holothurians that are long, cylindrical forms divide across 
the body and, therefore, in a structural plane at right angles to that of 
the brittle-stars. It may be claimed that in all these cases the plane 
of division is that in which the animal is most likely to be broken 
in two by external agents, but this is, I think, only a coincidence, 
and the result is really due to internal conditions. The division is 
brought about in most cases, and perhaps in all, by the contraction 
of the muscles ; and the arrangement of the muscles in connection 
with the form of the body is the real cause of the phenomenon. 

Returning to the general question of the occurrence of the process 
of division in the different groups, we find that in nearly all of them 
in which self-division occurs it is found in a number of different 
forms in the same group. The process seems to be characteristic 
of whole groups rather than of species, and so far as evidence of this 
sort has any value it points to the conclusion that the process is not 
necessarily a special case of adaptation to the surroundings, because 
the species that divide may live under very diverse conditions. 

A further examination of the facts throws a certain amount of 
light on the relation between the processes of self-division and of 
regeneration. The following questions may serve to guide us in our 
examination : — 

(i) Is regeneration found only in those groups in which self-divi- 
sion takes place as a means of propagation ; or, conversely, does 
self-division only occur in those groups that have the power of 
regeneration } 

(ii) Is regeneration confined, in the groups that make use of self- 
division as a means of propagation, to those regions of the body 
where the self-division takes place } 

(iii) Is regeneration as extensive in the groups that do not propa- 
gate by self -division as in those that do } 

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146 REGENERATION 

(iv) Can we account, in any way, for the presence of self-division 
in certain groups, and for its absence in others ? 

(v) What relation exists between the forms that prepare for sub- 
sequent self-division and those that do not ? 

The first question is easily answered. Regeneration is also found 
in nearly all the other groups that do not propagate by self-division, 
■*-as, for instance, the moUusks, vertebrates, etc. The second half of 
the question may also be answered. All the groups that propagate 
by self-division have also the power of regeneration.^ 

In answer to the second question there is ample evidence showing 
that regeneration is by no means confined to those regions of the 
body in which the self-division occurs. 

In answer to the third question, it may be stated that although, 
in the groups that propagate by self-division, regeneration may be 
present in nearly all parts of the body, the same phenomenon occurs 
in other groups that do not propagate by division. 

The fourth question offers many difficulties, and our answer will 
depend largely upon what we mean by ^^ accounting for^^ the process 
in certain groups. If the question is interpreted to ask, Why does 
an animal divide t no answer can be given. If it is meant to ask, Can 
we see how the process would be difficult, or even impossible, in cer- 
tain groups and not in others } then an approximate answer may be 
given, or at least an hypothesis formed. In the first place, the power 
of regeneration must be present in the region at which the self- 
division takes place in order that the result may lead to the formation 
of new individuals, or else be acquired in that region along with the 
acquirement of the means for division. A leech is not much more 
complicated than a marine annelid, yet it has little or no power of 
regeneration ; hence, perhaps, propagation by division could not be 
acquired by the leeches until they had first acquired the power to 
regenerate. In the second place, in certain forms a separation of the 
body into two parts would lead to the death of one or of both parts, 
owing to the dejiendence of the different regions upon each other. 
In forms like the vertebrates, insects, Crustacea, etc., we can readily 
see why this would be the case. Hence propagation by means of 
self-division could not be acquired, since the division itself would 
lead to the destruction of the organism. In the third place, the 
structure of the body may be such that the process of self-division 
would be mechanically impossible. A hard outer coat, like that 
of the sea-urchin, combined with a weak development of the mus- 

1 The proglottids of the cestodes seem to be an exception, but they are little more than 
sacs filled with embryos at the time of their separation. How far regeneration may take 
place in the scolex, or young proglottids, is not known, but it is not improbable that some of 
the abnormal forms that have been described may be due to regeneration. 



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SELF-DIVISION AND REGENERATION I47 

culature of the body, would effectively prevent the self-division of 
the animal. 

The fifth question has many sides. It involves us on the one 
hand in a historical question of the origin of self -division, and on the 
other hand in a discussion of the stimulus that brings about, not only 
the division, but the changes that precede the division in those cases 
in which the new part develops before division takes place. 

Several zoologists have held that the process of self-division fol- 
lowed by regeneration has been the starting-point for the process of 
propagation preceded by regeneration. Von Kennel, for instance, 
maintains that self-division in some of the annelids has arisen in this 
way. He says: " We recognize everywhere in the animal kingdom the 
power of organisms to replace lost parts, and we call this regenera- 
tion. It may be developed in very different degrees in animals, and, 
as a rule, only those parts of the body have the power of regenera- 
tion that still possess the organs that are essential for independent 
existence. The higher the organization of the animal, so much the 
less is its power of regeneration, perhaps, because the division of 
labor of the different organs has gone so far that extensive injuries 
cannot be repaired. . . . There is no doubt that this power is adap- 
tive, in a high degree, to preserve the species under unfavorable con- 
ditions, so that they are much better off in the battle for existence 
than are the animals that live under the same conditions but have 
not the power of regeneration. . . . The power of regeneration that 
gives the animal a better chance in the battle for existence and, there- 
fore, makes more certain the continuance and the distribution of the 
species will be, as is well known from numerous observations, in a 
high degree inherited, indeed even increased so that its descendants 
will possess that power in a higher degree than their forefathers ; and, 
in consequence, a much smaller stimulus (motive) suffices, than at 
first, to bring about the division of the parts," After showing, accord- 
ing to the usual formula, that the process of regeneration is useful, 
and, tlierefore, would come under the guidance of natural selection, 
von Kennel proceeds to show how the result is connected with an 
external stimulus!- He asks: "Can accidental injuries account for 
the result (viz. for the division in lumbriculus, planarians, and star- 
fish), since how few starfish are there with regenerating arms in com- 
parison with the enormous number of uninjured individuals.? Should 
we not rather look for the external stimuli that have initiated the pro- 
cess of self-division } " " Animals that have developed the power of 
regeneration by a long process of inheritance will have acquired along 
with this the property of easier reaction to all external adverse condi- 
tions. In arsense the sensitiveness for such stimuli is sharpened, and 
the animal responds at once by breaking up. In the same way the 



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148 REGENERATION 

ear of a good musician becomes more sensitive through practice. If 
we think of the same stimulus as regularly recurring, and as always 
answered in the same way, then we may look upon it as a normal 
condition of the life of the animal and its response as also a normal 
process in the animal. If, for instance, the breaking into pieces of 
lumbriculus is a consequence of the approach of cold weather or of 
other external conditions, then the organization of this animal must 
react by breaking up in consequence of its adaptation to the condi- 
tions acquired through heredity. The self-division becomes a normal 
process under normally recurring conditions. If the organism has 
been accustomed to respond through numerous generations, and, 
therefore, its sensitiveness has become highly developed, it will be 
seen that it may be influenced by the slightest change in the unfavor- 
able conditions, and although, at first, the change may not be suffi- 
ciently strong to cause the animal to divide, yet the introductory 
changes leading to the division may be started, which will in turn 
make the division, when it occurs, easier and the animal that pos- 
sesses this responsiveness more likely to survive. This would be the 
case if a slow process of constriction took place, so that, at the time 
of separation, no wounds of any size are formed." " By a further 
transfer of the phenomenon, a partial, or even a complete, regeneration 
may set in before division takes place.*' " We find changes like this 
in the series of forms, Lumbriailiis^ Ctcnodrihis monostylos, Cteno- 
drihis pardalis^ Nais, Clicetogaster. It appears in a high degree 
probable that the series has originated in the way described. Per- 
haps zoologists will find after some thousands of years that lumbricu- 
lus propagates as does nais at present." In this way von Kennel 
tries to show how the process of regeneration, that takes place before 
division, has been evolved from a simple process of breaking up in 
response to unfavorable conditions. The imaginary process touches 
on debatable ground, to say the least, at every turn, and until some of 
the principles involved have been put on a safer basis, it would be 
unprofitable to discuss the argument at any length. 

We should never lose sight of the fact that the arranging of a series 
like that beginning with lumbriculus and ending with chaetogaster is a 
purely arbitrary process and does not rest on any historical knowledge 
of how the different methods originated or how they stand related, and 
no one really supposes, of course, that these forms have descended 
from each other but at most that the more complicated processes may 
have been at first like those shown in other forms. Even this involves 
assumptions that are far from being established, and it seems folly 
to pile up assumption on top of assumption in order to build what is 
little more than a castle in the air. 



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REGENERATION AND BUDDING 1 49 

REGENERATION AND BUDDING 

In several groups of animals a process of budding takes place 
that presents certain features not unlike those of self-division. It 
is difficult, in fact, to draw a sharp line between budding and self- 
division, and although several writers have attempted to make a dis- 
tinction between the two processes, it cannot be said that their 
definitions have been entirely successful. It is possible to make a 
distinction in certain cases that may be adopted as typical, but the 
same differences may not suffice in other cases. For instance, the 
development of a new individual at the side of the body of hydra is a 
typical example of budding, while the breaking up of lumbriculus or of 
a planarian into pieces that form new individuals is a typical example 
of division. In a general way the difference in the two processes 
involves the idea that a bud begins as a small part of the parent ani- 
mal, and increases in size until it attains a typical form. It may 
remain permanently connected with the parent, or be separated off. 
By division we mean the breaking up of an organism into two or 
more pieces that become new individuals, the sum-total of the 
products of the division representing the original organism. Von 
Kennel first sharply formulated this distinction, and it has been also 
supported by von Wagner, who has attempted to make the distinc- 
tion a hard and fast one ; ^ but as von Bock has pointed out, there 
are forms like pyrosoma and salpa in which the non-sexual method 
of propagation partakes of both peculiarities, and in Syllis ramosa the 
individuals appear to bud from the sides, while in other annelids a 
process of division takes place. Von Bock assumes, therefore, as 
more probable, that budding and self-division are only different phe- 
nomena of the same fundamental process. It might be better, I 
think, to go even further in order to clear this statement from a pos- 
sible historical implication, and state only that the two processes 
involve some of the same factors. 

Budding occurs in several groups of the animal kingdom. There 
are numerous cases in the protozoa, such, for instance, as that in 
noctiluca. In the sponges buds are formed that go to build up a col- 
ony in most instances. In the ccelenterates cases of lateral budding are 
found in nearly all the main groups, and in one and the same indi- 
vidual, as in the scyphistoma of aurelia, in fact both budding and 
division occur. In the polyzoa, in the ascidians, and in cephalodiscus 
lateral budding takes place. In the rhabdocoel turbellarians, and in 
some of the annelids, we find chains of new individuals produced by 
a process that is often spoken of as budding. It is convenient, how- 
ever, to distinguish these cases of axial budding from those of lateral 

^ Except for the protozoa. 

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1 50 REGENERA TION 

budding; for, while they both involve an increase in the products 
over that of the original animal, the axial relations in lateral buds are 
established in a new plane, while in axial budding the main axis of 
the new animal is a part of that of the old, and this difference may 
involve different factors. The process of budding does not occur in 
the insects, spiders, crustaceans, moUusks, ctenophores, brachiopods, 
nematodes, vertebrates, or in several other smaller groups. 

This examination shows that there are groups in which both pro- 
cesses take place, viz. ccelenterates, planarians, annelids ; and others 
in which budding alone takes place, viz. ascidians, polyzoa, cephalo- 
discus; and one group at least in which division, but not budding, 
takes place, the echinoderms. It is obvious that from the occurrence 
of the process of budding in the animal kingdom we cannot infer 
anything as to its relation to division or to regeneration. 

It has been pointed out that in the flowering plants, in which the 
growth takes place by means of buds, the power of terminal regen- 
eration is very slightly developed, and its absence is sometimes ac- 
counted for on the ground that the new growth takes place by means 
of the development of lateral buds. If by this statement it is meant 
that buds being present the suppression of regeneration in other 
regions may occur, then there may be a certain amount of truth 
in the statement. If, however, it is intended to mean that be- 
cause a plant has acquired the power of reproducing new parts by 
means of buds it has, therefore, lost the power to regenerate in other 
ways (or has never developed the power to regenerate), then the 
argument is, I think, fallacious ; for we find even in flowering plants 
that the new buds sometimes arise from the new part, or callus, 
that forms over the cut-end, and this process resembles a real regen- 
erative process. We also find that hydroids that produce lateral 
buds also regenerate freely from an exposed end. But we are at 
present so much in the dark in regard to the causes that bring about 
budding in organisms that a discussion of the possibilities would 
hardly be profitable. 

AUTOTOMY 

• 

The process of autotomy differs only in degree from the process 
of self-division. In autotomy the part thrown off does not produce 
a new animal. The breaking off of the tail of the lizard at the base, 
if the outer part is injured, is an example of a typical process of 
autotomy. The throwing off of the crab's leg, if the leg is injured, is 
also another typical case of autotomy. There is a definite breaking- 
joint at the base of the crab's leg at which the separation always 
takes place (Fig. 45, A i-i). The breaking-joint is in the middle of 
the second segment from the base of the leg, where there is found, 



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AUTO TO MY 



151 



on the outside of the leg, a ring-like groove that marks the place of 
rupture. A comparison of the legs of the crab with the walking 
legs of the crayfish, or of the lobster, shows that the groove in the 
crab's legs corresponds to a joint in the legs of the two other forms. 
In the crayfish and lobster the walking legs generally break off at 
this same level, although by no means as easily or with as much 
certainty as in the crab. The first pair of legs of the crayfish and 






Fig. ^5. — A. After. Andrews. Base of leg of crab to show breaking-joint, i-i. B, After Fre- 
dericq. Diagram of leg of crab to show how autotomy takes place. C, After Andrews. 
Longitudinal section of base of leg to show in-turned chiunous plate at breaking-joint. 

lobster, carrying the large claws, have also a breaking-joint at the 
base of the leg similar to that in the crab's leg, and these legs break 
off in the living animal always at the breaking-joint. 

Reaumur first recorded that if the leg of a crayfish or of a crab is 
cut off outside of the breaking-joint it is always thrown off later at 
the breaking-joint. Fredericq has made a careful examination of the 
way in which the leg is thrown off in the crab, Carcinus mcenas. 
He found that the breaking does not take place at the weakest part 

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1 5 2 REGENERA TION 

of the leg; for the leg of a dead crab will support a weight of 3 J to 
5 kilograms, which represents about one hundred times the weight of 
the crab's body. When the weight is increased to a point at which the 
leg breaks, it does so between the body and the first segment or 
between the first and second segments. When it breaks off in this 
way, the edges are ragged and are left in a lacerated condition ; but 
when the leg is thrown off by the animal at the breaking-joint, there 
is left a smooth surface covered over, except in the centre, by a 
thin cuticle. Through the opening in the centre of this cuticle a 
nerve and a blood vessel pass to the distal part of the leg. Very 
little bleeding takes place when the leg is thrown off, but if the leg 
is cut off or broken off at any other level the bleeding is much 
greater. Fredericq studied the physiological side of the process and 
found that it is the result of a reflex nervous act. He found that if 
the brain of the animal is destroyed the leg may still be thrown off, 
but if the ventral cord is destroyed the reflex action does not take 
place. The reflex is brought about ordinarily by an injury to the 
leg that starts a nerve impulse to the ventral nerve-cord, and from 
this a returning impulse is sent to the muscles of the same leg, 
causing the muscles in the region of the breaking-joint to contract 
violently, and the result of their contraction is to break off the leg. 
If the muscles are first injured, the leg cannot be thrown off. Andrews, 
who has studied the structure of the breaking-joint in the spider- 
crab, has found that there is a plane of separation extending inwards 
from the groove on the surface. This plane is made by a narrow 
space between two chitinous membranes that are continuous at their 
outer ends with the general chitinous covering of the leg (Fig. 45, C\ 
When the leg breaks off, one-half of the double membrane is left 
attached to the base of the leg and the other to the part that is lost. 
This in-turned membrane seems to correspond to the in-turning of 
the surface cuticle in the region of the joints. The arrangement of the 
muscles at the breaking-joint is shown in Fig. 45, B, The upper 
muscle is the extensor muscle of the leg, and through its contraction 
the breaking off takes place. When it contracts the leg is brought 
against the side of the body, which is supposed to offer the resistance 
necessary to break off the leg. If the leg is held by an enemy, 
this may offer sufficient resistance for the muscle to bring about the 
breaking. 

In many crabs the leg is not thrown off if simply held, but only 
after an injury. Even the most distal segment may be cut off and 
the leg remain attached, and sometimes it is not lost after the distal 
end of the next to the last segment is cut off. If a crab is tejhered 
by one leg it will not throw off its leg in order to escape, unless, in 
the crab's excitement, the leg is twisted or broken. How^ generally 

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AUTO TOM Y 153 

this holds for all crabs cannot be stated. Herrick says : " Uninten- 
tional experiments in autotomy have often been made by tethering 
a lobster or a crab by its large claws. The animal, of course, escapes, 
leaving only its leg behind. When lobsters are drawn out of the water 
by the claws, or when a claw is pinched by another lobster, or while 
they are handled in packing, especially for the winter market, they 
often * cast a claw,' and the transportation of lobsters at this season 
is said to be attended by considerable loss in consequence." The 
large claws of the lobster are quite heavy, the base relatively small 
at the breaking-joint, and it may be that simply the weight of the 
claw, when out of the water, may strain the leg so that it breaks 
off, — the leg being injured by its own weight. The lobster seems to 
lose its claws quite often under natural conditions. Rathburn ^ states 
that "out of a hundred specimens collected for natural history pur- 
poses in Narragansett Bay in 1880, fully 25 per cent had lost a claw 
each, and a few both claws." Herrick ^ records that "in a total of 
725 lobsters captured at Woods HoU in December and January, 
1 893-1 894, fifty-four, or 7 per cent, had thrown off one or both 
claws." 

The autotomy of the arms of the starfish has been often ob- 
served.^ The arms are thrown off very near the base in many forms. 
If the animal is simply held by the arm it does not break off, but if 
injured it constricts and falls off. The lost arm does not regenerate 
a new starfish in most forms, but, as stated on page 102, there are 
recorded some cases in which the arm seems to have this power. 
King has found that out of a total of 1914 starfish (-^j/m^i* vulgaris) 
there were 206, or 10.76 per cent, that had new arms, and all of 
these, with one exception, arose from the base of the arm. The 
growth of the new- arm from the base takes place more rapidly, as 
shown in Fig. 38, A, than when the arm is regenerated from a more 
distal level ; but in the latter case the arm, despite its slower growth, 
may complete itself before another does that originates at the same 
time from the base of the old arm. There is, therefore, in this 
respect no obvious advantage, so far as regeneration is concerned, 
in throwing off the injured arm nearer to the disk. 

In the brittle-stars (ophiurians) the arm breaks off with greater 
ease and at any level. If the arm is simply held and squeezed, it 
will, in some forms, break off just proximal to where it is held. If 
the broken end is again held, another small piece breaks off, and in 
this way the arm may be autotomized, piece by piece, to its very base. 

* The Fisheries and Fishing Industries of the United States, Washington, 1887. 
« "The American Lobster," Bull, U. S. Fish Comm,, 1895. 

* Reaumur in 1742 records the first observations. Spallanzani also described the pro- 
cess, and many later writers have examined it. ^-^ ^ 

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154 REGENERATION 

Regeneration may take place from any region, but, as yet, no obser- 
vations have been made on the relative rate of growth of the new 
arm at different levels. 

One of the most remarkable cases of autotomy is that in holothu- 
rians, in which the Cuvierian organs, and even the entire viscera, may 
be ejected when the animal is disturbed. A new digestive tract is 
regenerated.^ 

It is known that several of the myriapods lose their legs at a defi- 
nite region near the base, and that they have the power of throwing 
off the leg in this region if "it is injured. I have often observed that 
the legs of Scutigera forceps are thrown off if they are held or injured, 
and even when the animal is thrown into a killing fluid. Amongst the 
insects the plasmids or walking-sticks also throw off their legs at a 
definite joint, as described by Scudder, and more recently by Bor- 
dage, and still later by Godelmann. New legs are regenerated 
from the stump of the old leg, as has long been known.^ Other 
insects do not have the power of throwing off their legs, and we have 
only a few observations that show that the legs if lost can be regen- 
erated. It is known in the cockroach that the tarsus can regenerate 
if lost or if cut off, and that fewer segments are regenerated than are 
present in the normal animal. Newport found that the true legs (ff a 
caterpillar are regenerated during the pupa stage if they have been 
previously cut off. 

A further example of autotomy is found in the white ants, which 
break off their wings at the base after the nuptial flight. There 
exists a definite and pre-formed breaking-plane in this region. 
The true ants also lose their wings after the nuptial flight, but there 
does not seem to be a definite plane of breaking, so that the process 
can scarcely be called one of autotomy. These cases also differ from 
the other cases of autotomy in that the lost parts are not renewed. 

It has been observed ^ that if the leg of tarantula is cut off at any 
other place than at the coxa, the animal bites off the wounded leg with 
its jaws down to the coxa. In other spiders this does not occur, 
although Schultz has observed that when the legs are lost under nat- 
ural conditions they are found broken off in most cases at the coxa. 
Schultz has also found that the legs regenerate better from this 
region than from any other. It would be rash, I think, to conclude 
without further evidence that the habit of tarantula to bite off a 
wounded leg down to the coxa has been acquired in connection with 
the better regeneration of the leg at this place. It is possible that 
the injury may excite the animal to bite off the leg as far as possible, 
which might be to the coxal joint. It would certainly be very remark- 

* The phenomenon has been obaerved by Dalyell, Semper, Minchin, and others. 
« MuUer, Elements of Physiol(^, 1837. « By Wagner ('87)^ 

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THEORIES OF AUTOTOMY 155 

able if this spider had acquired the habit in connection with the better 
regeneration of the leg at the base, since the leg can presumably also 
regenerate at any level, as in the epeirids. 

In this same connection I may record that in the hermit-crab I 
have often observed that when a leg is cut off outside of the break- 
ing-joint, if the leg is not thrown off at once, the claws of the first 
legs catch hold of the stump and, pulling at the leg, offer sufficient 
resistance for the leg to break off at the breaking-joint I cannot 
believe that this instinct has anything to do with the better regenera- 
tion of the leg at the coxal joint, however attractive such an hypothesis 
may appear. 

THEORIES OF AUTOTOMY 

A number of writers have pointed out that under certain condi- 
tions it is an obvious advantage to the animal to be able to throw off 
a portion of the body and thereby escape from an enemy. It has 
been suggested that if a crab is seized by the leg, the animal may 
save its life at times at the expense of its leg ; and since the crab has 
the power of regenerating a new leg, it is the gainer in the long run 
by the sacrifice. The holothurian, that ejects its viscera, has been 
supposed to offer a sufficient reward to its hungry enemy, and escapes 
paying the death penalty, at the expense of its digestive tract. Thus, 
having shown that the process of autotomy is a useful one, it is 
claimed that it must have been acquired through a process of natural 
selection ! An equally common opinion is that autotomy is an adap- 
tation for regeneration, since in certain cases, as in that of the crab's 
leg, better conditions for subsequent regeneration occur at the break- 
ing-joint than when the amputation takes place at any other region. 
Since less bleeding takes place when the crab's leg is thrown off at 
the breaking-joint, and since the wound closes more quickly when 
the arm of the starfish is lost at the base, it is assumed that we have 
in both cases an adaptation to meet accidents, and that the adaptation 
has been acquired by natural selection. 

A consideration of these questions involves us once more in a dis- 
cussion of the theory of natural selection. An attempt has been made 
in another place (pages 108-1 10) to show that we are not justified in 
assuming that because a process is useful, therefore it must have been 
acquired by means of natural selection. Even if it were granted that 
the theory of natural selection is correct, it does not follow that all 
useful processes have arisen under its guidance. We may, therefore, 
leave the general question aside, and inquire whether the process of 
autotomy could have arisen through natural selection (admitting that 
there is such a process, for the sake of the present argument), or 
whether autotomy must be due to something else. ^ I 

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156 REGENERATION 

If we assume that the leg of some individual crayfishes or crabs, 
for example, broke off, when injured, more easily at one place than at 
another, and that regeneration took place as well, or even better, from 
this region than from any other, and if we further assume that those 
animals in which this happened would have had a better chance of 
survival than their fellows, then it might seem to follow that in time 
there would be more of this kind of animal that survived. But even 
these assumptions are not enough, for we must also assume that this 
particular variation was more likely to occur in the descendants of 
those that had it best developed, and that amongst those forms that 
survived, some had the same mechanism developed in a still higher 
degree, and, the process of selection again taking place, a further 
advance would be made in the direction of autotomy. This, I think, 
is a fair, although brief, statement of the conventional argument as to 
how the process of natural selection takes place. But let us look 
further and see if the results could be really carried out in the way 
imagined, shutting our eyes for the moment to the number of suppo- 
sitions that it is necessary to make in order that the change may 
occur. It will not be difficult, I believe, to show that even on these 
assumptions the result could not be reached. In the first place, the 
crabs that are not injured in each generation are left out of account, 
and amongst these there will be some, it is true, that have the particu- 
lar variation as well developed as the best amongst those that were 
injured, and others that have the average condition, but there will be 
still others that have the possibilities less highly developed, and the 
two latter classes will be, on the hypothesis, more numerous than 
those in the first class. The uninjured crabs will also have 
an advantage, so far as breeding and resisting the attacks of their 
enemies are concerned, as compared with those that have been injured, 
and in consequence they, rather than the injured ones, will be more 
likely to leave descendants. Even if some of those that have been 
injured, and have thrown off the leg at the most advantageous 
place, should interbreed with the uninjured crabs, still nothing, or 
very little, can be gained, because, on Darwinian principles, inter- 
crossing of this sort will soon bring back the extreme variations 
to the average. 

The process of natural selection could at best only bring about 
the result provided all crabs in each generation lose one or more of 
their legs, and amongst these only the ones survive that break off the 
leg at the most advantageous place ; but no such wholesale injury 
takes place, as direct observation has shown. At any one time only 
a small percentage, about ten per cent, have regenerating legs, and 
as the time required completely to regenerate a leg, even in the sum- 
mer, is quite long, this percentage must give an approximate idea of 

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THEORIES OF A UTOTOMY 1 5 7 

the extent of exposure to injury. It is strange that those who assert 
off-hand that, because autotomy is a useful process, therefore it must 
have been acquired by natural selection, have not taken the pains to 
work out how this could have come about. Had they done so, I can- 
not but believe they would have seen how great the difficulties are 
that stand in the way. 

A further difficulty is met when we find that each leg of the crab 
has the same mechanism. If we reject as preposterous the idea that 
natural selection has developed in each leg the same structure, then 
we must suppose that a crab varies in the same direction in all its legs 
at the same time ; and if this is true it is obvious that the principle of 
variation must be a far more important factor in the result than the 
picking out of the most extreme variations. The same laws that 
determine that one individual varies in a useful direction farther than 
do other individuals may, after all, account for the entire series of 
changes. If it be replied that natural selection does not take into 
account the causes of the differences of individual variation, this is 
to admit that it avowedly leaves out of account the very principles 
that may in themselves, and without the aid of any such supposed 
process as natural selection, bring about the result. The Lamarckian 
principle of use and disuse does not give an explanation of autotomy, 
since the region of the breaking-joint is not the weakest region of the 
leg, or the place at which the leg would be most likely to be injured. 

We cannot assume autotomy to be a fundamental character of liv- 
ing things, since it occurs only under special conditions, and in special 
regions of the body. While it might be possible to trace the autot- 
omy of the legs of the Crustacea, myriapods and insects, to a common 
ancestral form, yet this is extremely improbable, because the process 
takes place in only a relatively few forms in each group. The au- 
totomy of the wings of white ants that takes place along a preexisting 
breaking-line must certainly have been independently acquired in this 
group. The breaking off of the end of the foot in the snail helica- 
rion is also a special acquirement within the group of mollusca. 

Bordage has suggested that the development of the breaking-joint 
at the base of the leg of phasmids has been acquired in connection with 
the process of moulting. He has observed that during this period the 
leg cannot, in some cases, be successfully withdrawn through the 
small basal region ; and hence, if it could not break off, the animal 
would remain anchored to the old exoskeleton. It escapes at the 
expense of losing its leg. The animal, having acquired the means of 
breaking off its leg under these conditions, might also make use of the 
same mechanism when the leg is held or injured, and thereby escape 
its enemy. The fact that the crayfish has a breaking-joint only for 
the large first pair of legs would seem to be in favor of thisiBterprej- 

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1 5 8 REGENERA TION 

tation, but the crab has the same mechanism for the slender walking 
legs, that one would suppose could be easily withdrawn from the old 
covering. It should also be remembered that we do not know 
whether the breaking-joint at the base of the leg of the crab and 
of the crayfish would act at the time when the leg is being with- 
drawn from the old exoskeleton, unless the leg were first injured 
outside of the joint. 

Our analysis leads to the conclusion that we can neither account 
for the phenomenon of autotomy as due to internal causes alone in 
the sense of its being a general property of protoplasm, nor to an 
external cause, in the sense of a reaction to injury or loss from 
accident. There would seem then only one possibility left, namely, 
that it is a result of both together, or in other words, a process that 
the animal has acquired in connection with the conditions under 
which it lives, or in other words, an adaptive response of the organism 
to its conditions of life. 

We are not, however, able at present to push these questions 
farther, for, however probable it may seem that animals and plants 
may acquire characteristics useful to them in their special conditions 
of Ufe, and yet not of sufficient importance to be decisive in a life and 
death struggle, still we cannot, at present, state how this could have 
taken place in the course of evolution. For, however plausible it 
may appear that the useful structure has been built up through an 
interaction between the organism and its environment, we cannot 
afford to leave out of sight another possibility, viz. that the struc- 
ture or action may have appeared independently of the environ- 
ment, but after it appeared the organism adopted a new environment 
to which its new characters made it better suited. If the latter alter- 
native is true, we should look in vain if we tried to find out how the 
interaction of the environment brought about the adaptation. The 
relation would not be a causal one, in a physical sense, but the out- 
come of a different sort of a relation, viz. the restriction of the organ- 
ism to the environment in which it can remain in existence and leave 
descendants. 



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CHAPTER IX 

GRAFTING AND REGENERATION 

By uniting parts of the same or different animals, or of plants, 
there is given an opportunity of studying a number of important 
problems connected with the regeneration of the grafted parts. 
Trembley's experiments in grafting pieces of hydra are amongst 
the earliest recorded cases of uniting portions of different animals, 
although in plants the process of grafting has been long known. ^ 
Trembley found that if a hydra is cut in two, the pieces can be 
reunited by their cut-surfaces, and a complete animal results. No 
regeneration takes place where the union has been made. He also 
succeeded in uniting the anterior half of one individual with the 
posterior half of another individual, and again produced a single 
individual. He failed to obtain a permanent union between different 
species. 

More recently, Wetzel has carried out a number of different 
experiments in uniting pieces of hydra. He found that if two 
hydras are cut in two, the two anterior pieces may be united by the 
aboral cut-surfaces (Fig. 46, B), and the two posterior pieces may 
also be united by their oral cut-surfaces (Fig. 46, A). The fuision 
of these " like-ends " takes place as readily as when unlike ends are 
brought in contact, as in Trembley's experiments. Subsequently, 
however, regenerative changes take place. When, for instance, two 
anterior pieces are united by their aboral ends, there develop after 
two or three days one or two outgrowths, at or near the line of union, 
that become new feet, and the two individuals may subsequently 
separate. When two posterior pieces are united by their oral sur- 
faces, a double circle of tentacles generally develops, one on each 
side of the line of union. The pieces then pinch apart and produce 
two hydras.^ In another experiment the head and a part of the foot 
were cut from a hydra, and the head was turned around and grafted 
by its aboral surface upon the aboral surface of the middle piece. 
Another animal was cut in two in the middle, and the posterior half 
was grafted by its oral end to the oral end of the middle piece. In 

* For references to the literature on grafting in plants see Vochting (*84). 
' In one case they separated only after three months. 

159 



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i6o 



REGENERATION 



this way a new, artificial individual was made, as shown in Fig. 46, C, 
with the middle part of the body in a reverse direction as compared 
with the orientation of the two end-pieces.^ The union of the three 
pieces was so perfect that not even a swelling or a constriction indi- 
cated the places of fusion. After six days a normal bud appeared at 
the region of union of the posterior and middle pieces, that gave 
rise to a new hydra, which separated after a few days. The com- 



A « W% Jj\/|f 




Fig. 46. — A. Two posterior pieces of hydra united by their oral ends. B. Two anterior pieces 
of hydra united by their aboral ends. C. A " long hydra " made by uniting three pieces ; the 
middle piece reversed. D. After Peebles. Two posterior pieces of brown hydra united by 
oral ends, and one cut off near union. A new anterior end developed from the cut, aboral sur- 
face. F, After Peebles. Union of a nutritive and a protective polyps of hydractinia. Subse- 
quently former cut off at line, i-i. E. Union of two posterior pieces of hydra by oral ends. 
Subsequently one piece cut off at line, 2-2. E^. New head regenerated in region of union, 
and a foot from aboral cut-end. E^, E^, Fusion of two parts with a single hydra. 

pound animal was healthy and ate many daphnias. It was kept under 
observation for twenty-four days, and appeared normal, giving off 
several more buds. 

In other experiments of this same sort a foot generally developed 
where the two aboral surfaces came together, and the head-end sepa- 
rated from the rest of the piece. In another case a mouth and tenta- 
cles appeared at the place at which the oral ends had united. 

^ This and other experiments were carried out by pushing the pieces on a bristle. 



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GRAFTING AND REGENERATION l6l 

In a different kind of experiment, the anterior ends of two hydras 
were cut off and united by their aboral surfaces; then one of the 
components was cut in two, just back of the circle of tentacles. 
After five days two short, hook-like processes appeared at the cut, 
oral end. They produced a foot, by means of which the animal 
fixed itself. In this case it will be seen that a foot developed from 
an oral end. The result might not in itself be considered sufficient to 
show whether the development of a foot at the oral end of a piece is 
due to the influence of the other component, or is simply a case of 
heteromorphosis having no connection with the presence of the other 
component. Since heteromorphosis has never been observed in iso- 
lated pieces of hydra, the probability is that the result is in some way 
connected with the presence of the other component. Peebles has 
made a number of experiments, in which special attention was paid 
to this point. Fifteen anterior pieces were united in pairs by their 
aboral cut-surfaces, and then one component was cut in half, leaving 
an exposed oral end. Out of this number five pieces formed a new 
head at the cut-surface, and the pieces became attached by a foot, 
that developed at the region of union. Two others did not regener- 
ate at the cut-surface, but became fixed as before, and neither regen- 
erated nor became fixed at the cut-end. Three became attached at 
the cut, oral surface, but none of these developed a characteristic 
foot. The result shows, nevertheless, that some influence was present 
that inhibited the development of a mouth and tentacles at the oral 
cut-end, since these always develop in isolated pieces. In another 
series of experiments posterior ends were united by their oral sur- 
faces, and then one of the two pieces was cut in two (Fig. 46, E\ A 
new hypostome and tentacles developed at the region of union, and 
a foot at the aboral cut-surface, as shown in Fig. 46, E^. An organ- 
ism, with one mouth and a circle of tentacles, and two bodies and 
two feet, resulted. The bodies soon began to fuse together (Fig. 46, 
E^) into a single one, and when the fusion had extended to the region 
of the feet, they also fused into a single structure (Fig. 46, E^), so 
that a single hydra was produced. 

In another experiment, twenty-two posterior ends were united in 
the same way, and then one of the two components was cut in two. 
In five cases a single head developed on the aboral end of the smaller 
piece (Fig. 46, D). It is evident in this case that the union of the two 
pieces has been a factor in bringing about the development of an 
aboral head. Another of the grafts produced an aboral head, and also 
one in the region of union. The remaining sixteen grafts produced 
new heads, if they developed at all, only in the region of union. Pee- 
bles states that the regeneration of aboral heads takes place only when 
one component is cut off near the region of union of the two pieces. 

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1 62 REGENERA TION 

In general, it may be stated in regard to these experiments in 
hydra that when pieces are united in the same direction, that is, by 
unlike surfaces, a single individual is formed and no regeneration 
takes place where the union has been made, but when like surfaces 
are brought together, although perfect union may result, a process of 
regeneration takes place later, at or near the line of union. Eyen 
the presence of cut-surfaces at one or both cut-ends of the united 
components does not generally affect the result, although, in a few 
cases, it may change it, in so far that heteromorphic regeneration may 
take place from one piece. This sometimes leads to a suppression of 
regeneration at the line of union. The experiments do not show, 
perhaps, conclusively whether the heteromorphosis of the smaller 
component is due to the polarity of the larger component effecting a 
change in the smaller one, or whether the closing of the oral end of 
the smaller component (by its union with the other) brings about the 
result. All things considered, it seems to me that the larger compo 
nent has directly influenced the other. 

King has found that if two posterior pieces of hydra are united 
by the oral cut-surfaces, and then after they have fused both pieces 
are cut off near the line of fusion, there develops from the small 
piece a single hydra^ with a foot at one end and tentacles at the other. 
If only one of the pieces is cut off near the line of fusion, a new 
head develops from its oral surface, as Peebles had found. If two 
anterior ends are united by their aboral cut-surfaces, and then later 
both are cut off near the line of fusion, a single hydra develops from 
the small, double piece. If one of the components is cut off near 
the line of union, a foot develops from the oral cut-end. If in any 
of the cases the cut is made some distance from the line of union, 
then each cut-surface develops its typical structure. These experi- 
ments leave no doubt as to the influence of the larger piece on the 
smaller one. Especially interesting is the formation of one individual 
from two short pieces united in opposite directions. In this case we 
must suppose that one piece has the stronger influence on the combi- 
nation (perhaps because it is a little larger), and determines the polari- 
zation of the other piece. 

King finds that when two posterior pieces are united by their oral 
ends, regeneration of one or of two heads often takes place at the 
line of union (Fig. 47, 5, B^^ B^\ as Wetzel had found. If a dark 
green individual is united to a light green one, it can be seen that in 
many cases the new heads are formed by both components, as shown 
in Fig. 47, B^. Later one of the posterior ends is absorbed, and 
the halves may then separate (Fig. 47, B^, B^). If a number of 
pieces are united, as indicated in Fig. 47, E, a number of heads may 
be formed, and one or more of these may have a double origin. No 



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GRAFTING AND REGENERATION 



163 



evidences of separation of the pieces was observed in cases of this 
sort. 

In one experiment two posterior pieces were united by oblique 
surfaces, as shown in Fig. 47, C, and one of the two was afterwards 
cut across, as indicated by the cross-line. The subsequent re- 
generation that took place is shown in Fig. 47, C^. A head, com- 




FlG. 47. — After Kin^. A. Hvdra split in two, hangins^ vertically downwards. Later the halves 
completely separated. P, Two posterior ends united by oral surfaces. H^. Same; it regen- 
erated two heads, each composed of parts of both pieces. /A Absorption of one piece lead- 
ing to a later separation of halves. C. Two posterior ends united by oblique surfaces. Later 
one piece partially cut off, as indicated by line. C^. loiter still, two heads developed, one at 
A', the other at M. D. Similar experiment in which only one head developed, at M, E. Five 
pieces united as shown by arrows. Four heads regenerated, one being composed of parts of 
two pieces. 

posed of parts of both pieces, developed at the cut-surface M^ and 
another in the region N in Fig. 47, C, composed of material of one 
component. In another case, shown in Fig. 47, D, a head devel- 
oped only at the cut-edge, but it was made up of material from both 
components. 

A series of grafting experiments of another sort has been made 

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i64 



REGENERATION 



by Rand. A part of one hydra is grafted upon the side of another 
one in the following way. A groove is scratched in a film of soft 
paraffine covering the bottom of a dish filled with water. Another 
groove is made at right angles to the first one, and opening into it. 
A hydra (the stock) is placed in the first groove, and a wound made 
in its side with a knife. Another hydra is cut in two, and one piece 
(the graft) placed in the other groove, and its cut-surface brought 
into contact with the wound in the side of the first individual. If 
the operation is successful the exposed surfaces of the two hydras 






B* 



Fig. 48.— After Rand. A. Head of Hydra cut off. After eight days. A^. Same after thirteen 
days. Three tentacles misplaced. A^. Same after eighteen days. A^. Same after twenty- 
one days. Misplaced tentacles absorbed. B, Anterior end of Hydra fitsca, izjafted up>on 
side of body of another individual. Half an hour after operation. ^1. Same after four days. 
B^. Same after thirty-eight days. B^. Same, foot-region after forty-nine days. B*. Same 
after separating. Fifty-second day. 

quickly unite, and the combination may be taken out of the groove. 
If the piece grafted on the stock included about the anterior half 
of a hydra, a two-headed animal results, as shown in Fig. 48, B. 
Although the graft has been united to the side of the stock, it soon 
assumes an apparently terminal position (Fig. 48, B^). This is due 
to the graft sharing with the anterior end of the stock the common 
basal portion of the stock. A slow process of separation of the two 
anterior ends now begins, brought about by a deepening of the angle 
between the halves (Fig. 48, B^). This leads ultimately to a com- 



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CRAFTING AND REGENERATION l6S 

plete separation of the two individuals (Fig. 48, B^, B^\ Each may 
get a part of the original foot, or a new foot may arise on the graft 
as the division approaches the base. 

In other experiments only a small part ^of the foot-end was cut 
from the animal that served as the graft. The long anterior piece 
was grafted as before upon the side of the stock. After the two had 
united, the graft was cut in two, leaving a part of the graft attached 
to the stock. The part regenerated tentacles, and in two cases sub- 
sequently separated from the stock as in the first experiment. In a 
third case the graft was absorbed by the stock as far as the circle 
of new tentacles, but its subsequent fate was not determined. In a 
fourth case the graft did not regenerate its tentacles, and was com- 
pletely absorbed into the wall of the stock. The smaller the piece 
that is grafted on the stock the greater the chance that it will be 
absorbed, and furthermore short, broad rings are more likely to 
be absorbed than long, tubular pieces of the same volume.^ 

Rand's results show in general that when hydras are grafted 
together they regain the typical form in one of two ways, — either 
by separation into two individuals, or by the absorption of the smaller 
into the larger component. In the former case the result is brought 
about in the same way as when the anterior end is partially split in 
two and the halves subsequently separate. When the graft is ab- 
sorbed it is not clear whether the absorbed piece disappears or, as 
seems not improbable, forms a part of the wall of the stock. 

It is important to notice the difference between lateral buds and 
lateral grafts. The buds separate in the course of four or five days 
by constricting at the base, but this never happens in lateral grafts. 
Rand has also made some experiments with buds. He cut off the 
outer oral end of a bud, and grafted it back upon the stock in a new 
place. It did not separate from the stock as does a bud, but by 
a slow process of division it was set free in the same way as are 
lateral grafts. The proximal end of the bud, which was left at- 
tached, developed tentacles at its free end, constricted at its base, 
and was set free. The separation was, however, somewhat delayed. 
In another experiment a bud was split in two lengthwise, and the 
cut was extended so that the body of the parent was separated into 
two pieces. Twenty-four hours later it was found that each half-bud 
had closed in, and was much larger than when first cut. The half- 
bud, that was attached to the posterior end of the anterior piece, was 
constricting at its base, and subsequently it separated at its point of 

* Rand found that when a posterior piece was grafted by its cut, oral end to the side 
of another hydra that it was absorbed into the stock. In one case it moved down the whole 
length of the body of the stock and finally disappeared by absorption into the foot of the 
stock. 



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i66 



REGENERATION 



attachment. The other half of the bud, that had been left attached 
to the anterior end of the posterior piece, had swung around, so that 
its long axis corresponded to that of the posterior, parental piece. 
At first a slight constriction indicated the line of union of the two. 




A B C D E F G 

Fig. 49. — After Peebles. A, Grafting in Tkbularia mesenbryanthemum, A small piece of the 
stock taken from the region near the base, and grafted in a reversed direction on the oral end 
of a long piece. B. Same with distal tentacles in small piece, and proximal tentacles in large 
piece (modified from Peebles). C, Same. Formation of hydranth (original). D. Like ^-Z. 
Both pieces produce hydranths. E. Protrusion of hydranths of last. F, Piece of oral end 
cut off, turned around and grafted on oral end of long piece. A single hydranth produced. 
Distal tentacle from both components. G, A short piece from distal (oral) end of long piece 
cut off, and grafted by its proximal end to proximal end of the same long piece. 

but later this disappeared and a single hydra resulted. Whether 
the difference in the fate of the two half-buds is connected with their 
different polar relations to the parts of the parent, or is due to some 
other difference in the absorbing power of the anterior and posterior 
pieces, is not known. 

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GRAFTING AND REGENERATION 1 67 

Tubularia is not so well suited as hydra to show the influence 
of grafting on the united parts, since pieces of tubularia produce 
hydranths, both at the oral and aboral ends, although the latter 
hydranths take longer to develop. Peebles has shown, nevertheless, 
that grafting has an influence on the behavior of a piece. In order 
to show that the polarity of a small piece could be affected by a 
larger piece, the following experiment was carried out. After cutting 
off the old hydranth from the end of a stem, a short piece was then 
cut from the distal end of the same stem, turned around, and its oral 
end brought in contact with the oral end of the original piece, as 
indicated in Fig. 49, F, The two pieces, being held together for a 
few minutes, stuck together and subsequently united perfectly. 
From eighty-eight pieces united in this way the following results were 
obtained. Thirty-six formed a single hydranth at the end at which 
the grafting had been made. The distal row of tentacles appeared 
in the smaller reversed component, the proximal row in the larger 
piece (Fig. 49, E), The new hydranth pushed out later through the 
perisarc of the smaller piece (Fig. 49, C). In this experiment the 
smaller component was shorter than the average length of the hy- 
dranth-forming region. In two cases, in which the smaller component 
was larger, both circles of tentacles appeared in this piece. In six of 
the experiments the tips of the proximal tentacles arose from a part 
of the wall of the smaller piece, hence these tentacles had a double 
origin (Fig. 49, F\ In five of the unions the smaller as well as the 
larger component produced a hydranth ; the two were stuck together 
by their oral ends (Fig. 49, D, E). The remaining four unions gave 
somewhat different results. In three of these the smaller piece pro- 
duced only a part of a hydranth that remained sticking to the end of 
the hydranth formed by the larger component In the thirty-six 
cases in which the minor component took part in the formation of 
the single hydranth, the influence of the larger component was shown 
not only in reversing the polarity of the smaller component, although 
this might in part be accounted for by the closing of the oral end of 
the smaller piece, but also in the time of development, since the 
hydranth appeared sooner than does the aboral hydranth and at the 
same time as does the oral hydranth. 

In another series of experiments, a short piece was cut from the 
basal end of a long piece (three to four centimetres) and brought 
forward and grafted in a reversed position on the anterior end of 
tjie same long piece (Fig. 49, A), Of five unions of this sort, one 
produced a hydranth in each component, neither being reversed. 
Another of the pieces produced a hydranth partly out of each com- 
ponent (and at the same time another at the aboral end of the large 
piece). The other two pieces produced a single hydranth, apart of 

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1 68 REGENERA TION 

which came from the minor component and appeared before the 
aboral hydranth on the aboral end of the larger piece. This last 
result shows that the small piece from the basal end has been affected 
by the oral end in such a way that it develops more rapidly than it 
would have done had it remained a part of the basal end. 

In a third series of experiments a short piece (about a half of a 
millimetre) was cut from the anterior end of a long piece (one and 
five-tenths to two centimetres) and grafted in a reversed position on 
the posterior end of the same long piece (Fig. 49, G\ In four cases 
a hydranth developed only at the oral end of the lotig piece and none 
from the aboral end or from the short piece. Eight unions produced, 
however, in the region of the graft, a hydranth formed partly by 
each component. Later another hydranth developed at the oral end 
of the larger piece. The latter results are not convincing, but they 
may show that the small piece has hastened the development of the 
hydranth at the aboral end. 

Peebles has also made some experiments in grafting pieces of dif- 
ferent members of the colonies of hydractinia and podocoryne. The 
colony of the former is made up of three different kinds of individ- 
uals: the nutritive, the reproductive, and the protective hydroids. 
A series of preliminary experiments showed that if these individuals 
are cut into a number of pieces each piece regenerates the same kind 
of individual as that of which it had been a part. It was also 
observed that if pieces of the nutritive individuals were allowed to 
remain quietly on the bottom of the dish they sent out branching 
stolons, which stuck to the bottom of the dish, and from these stolons 
there arose later nutritive hydranths that stood at right angles to the 
surface. When pieces of the same kind of individuals are grafted 
together, the results are essentially the same as with tubularia. If 
pieces of different kinds of individuals are united, the opportunity 
is given of testing the possible influence of one kind on the other. 
Peebles united a nutritive and a protective polyp by the cut, aboral 
ends (Fig. 46, E\ and after they had grown together one of the 
polyps was cut off near the region of union, so that a small piece 
of a nutritive polyp was left attached to a protective polyp. When 
the piece of the nutritive polyp regenerated, it made a new nutritive 
polyp. The influence of the protective polyp was not apparent. If 
a nutritive and a reproductive polyp are united in the same way, and 
the latter cut in two near the line of union, a new reproductive polyp 
develops from the piece left attached to the nutritive polyp. Again 
there is shown no influence of the one on the other kind of polyp. 

Hargitt has also made a number of grafting experiments on other 
hydroids. His most interesting results are those in which parts of 
two medusae were united by holding their cut-surfaces together by 

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GRAFTING AND REGENERATION 169 

means of bristles passing through the individuals. Hargitt also finds 
that while in certain hydroids it is possible to bring about a union of 
oral with oral end, or aboral with aboral, or oral with aboral end of 
the same species,^ yet a permanent union between different species 
cannot be brought about. These results are in agreement with those of 
a number of writers who have recorded the difficulty or impossibility 
of uniting parts of different species of hydra. In a few instances it 
has been possible to unite temporarily a piece of a brown hydra with 
a piece of a green one, — as I have also seen accomplished, — yet the 
pieces subsequently separate. Wetzel succeeded in obtaining better 
results with two species of brown hydras. Hydra ftisca and Hydra 
grisea. In one experiment the head of Hydra grisea was grafted on 
the body (from which the head had been cut off) of Hydra fusca. 
After five hours the pieces seemed to have united. Later a constric- 
tion appeared at the place of union, and the head-piece produced 
a foot near the line of union, and the posterior piece produced 
a circle of tentacles at its anterior end. Eight days later, when the 
animal was being killed, it fell apart into two pieces. It was observed 
that during the period of union a stimulus to one piece was not car- 
ried over to the other. Wetzel's results seem to show that pieces of 
these two species of hydra unite at first, when brought together, as per- 
fectly as do pieces of the same species, but the union never becomes 
permanent, a constriction appearing later at the line of union, and the 
pieces separating in this region. These results indicate, it seems to 
me, that the factors that bring about the first union are different from 
those that make the grafted pieces one organic whole. Other results 
indicate that the union of oral to oral end, or aboral to aboral end, 
while at first as perfect as between unlike surfaces, nevertheless is 
less permanent than when unlike surfaces are united ; at least, sub- 
sequent regeneration is more likely to occur in the former than in the 
latter, and after this occurs the separation of the individuals often 
takes place. It seems, moreover, not improbable that a more per- 
manent union results when similar regions are united by unlike sur- 
faces, than when the union is at different levels. If, for instance, 
the anterior half of one hydra is united to the posterior half of 
another individual, the union is generally permanent ; but if one or 
both of the pieces are longer than half the length, so that a " long 
animal'* results, new tentacles, are more often formed at the oral 
end of one component, and the parts subsequently separate. It 
may be that, at present, the data are insufficient to establish this 
general rule, and no doubt other modifying influences must be also 
taken into account; but it is important that attention should be 
drawn to this side of the subject. 

^ Pieces from male and female colonies of the same species also unit^ 

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I70 



REGENERATION 



Grafting experiments in planarians have so far been carried out in 
only the two cases which I have described. In one of these the ante- 
rior ends of two short pieces of Bipalium kewense were united (Fig. 

50, A), Neither piece produced a 
head at the region of union. Later 
the pieces were cut apart by an 
oblique cut that passed across the 
line of union (Fig. 50, C\ so that 
each piece retained at its most an- 
terior end (at one side) a piece of 



LU 





I 



! 




Fig. 51. — Two pieces of Bipalium kewense 
united by posterior ends. Each regen> 
erated a head at anterior end. 

the Other individual in a reversed 
position. A head developed at the 
anterior (and lateral) end of each 
piece, in such a way that a part at 
least of the small reversed piece 
was contained in the new head 

Fig. 50. — A, Two pieces of Bipalium kewense / p: tc\ D\ In the Other case tWO 

united by anterior ends. B, C Later \'^ ^B' b^> -'^ )- m ine Oiner casc rwo 

stages of same. Line in C indicates how pieCCS of bipalium WCre United by 

pieces were cut apart, D. Two worms , . ^ . ^ ^ t- l 

produced by these pieces. All drawn to their posterior CUt-SUriaCCS. rl^ach 

^^^^' piece produced a new head at its 

free end, and the pieces greatly elongated, but remained sticking 
together (Fig. 51). 

A large number of experiments have been made by Joest in graft- 
ing pieces of earthworms. The cut-surfaces were held in contact by 
means of two or three threads passing through the body wall of each 
piece and tied across, so that the pieces were drawn together and 
held firmly in that position. Joest found that pieces of the same or 
of different individuals could be united in various ways, and the 
union become permanent. If the anterior end of one worm is united to 
the posterior end of the same, or of another worm, a perfect union is 



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GRAFTING AND REGENERATION 



171 



formed, and no subsequent regeneration takes place (Fig. 52, A\ 
Long worms can be made by uniting two pieces, each more than half 
the length of a worm, or by uniting three pieces, as shown in Fig. 52, C 
Short worms can be formed by cutting a middle piece from a worm, 
and uniting the anterior and posterior pieces (Fig. 53, D), Joest 
found that when a short worm is made in this way, so that no repro- 
ductive region is present, the new worm does not produce new repro- 
ductive organs. It is conceivable that new reproductive organs might 




• •»«»4«WII 



Fig. 52. — After Jocst. A, Union of two pieces of Allolobaphora terrestris in normal position. 
Twenty-two months after operation. B. Union of two pieces Lumbricus rubellus. Pieces 
turned 180° with respect to each other. C. Union of three pieces of A. terrestris to make a 
" long worm." D. Union of two worms (by anterior ends) from each of which eight an- 
terior segments had been removed. After three months. Regenerating two new heads. 
E. A small piece of Lumbricus rubellus grafted upon Allolobophora terrestris. Former re- 
generated an anterior end. 

have been produced either in the old segments, or by the formation 
of a new reproductive region between the two united pieces, but 
neither process takes place. In the long worms two sets of repro- 
ductive organs, etc., are present. This sort of union is, however, 
less permanent, as the worms often pull apart. 

Joest also united two posterior ends by their anterior surfaces. 
In many cases no regeneration took place, and, in the absence of a 
head, the combination is destined to die, although it may remain 
alive, without food, for several months. When two very long pieces 

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1 72 REGENERA TION 

were united by their anterior ends, — only eight segments being 
removed from each worm, — although perfect union took place at 
first, later one or two new heads generally developed at the region of 
union (Fig. 52, D\ When only one head developed it did not seem 
to belong to one of the components rather than to the other, and 
originated in the new tissue that appeared between the two pieces. 
These experiments, in which the anterior surfaces of two pieces are 
united, show also that the new head arises between the two pieces 
most often, if not exclusively, when the union is in the anterior ends 
of the worms. This corresponds with what is now known in regard 
to the development of new heads by isolated pieces, since there is less 
tendency to produce a head the farther posteriorly the cut has been 
made. At more posterior levels a tail and not a head is often regen- 
erated, as has been stated, on the anterior cut-surface. This forma- 
tion of a heteromorphic tail seems to have been suppressed in the 
pieces united in this region, except in one case,^ in which it appears, 
from Joest*s account, that a tail probably regenerated, although Joest 
speaks of it as a head. 

It is more difficult to unite two anterior ends by their posterior 
cut-surfaces, not because the surfaces refuse to unite, but because the 
two pieces crawl away from each other and pull apart. In one case, 
however, union of this sort was brought about. 

In all the combinations that have been so far described, the 
dorsal and ventral surfaces of both components were kept in the 
same direction, so that the ventral nerve-cord of one piece came in 
contact and fused with the nerve-cord in the other piece. Sometimes 
it may happen that the components are not quite in the same position, 
and the end of one nerve-cord may fail to abut against the other one. 
In such cases Joest thinks that regeneration is more apt to take place 
in the region of union, and he has carried out a series of experiments 
in which the pieces were intentionally united, so that they are not in 
corresponding positions. It is found that if one piece is turned so 
that the nervous system lies 90 degrees, or even 180 degrees (Fig. 52, 
B\ from that of the other piece, the union takes place just as when 
the pieces have the same orientation, except that the ends of the 
nerve-cords do not unite. Subsequent regeneration from one or from 
both components generally takes place in the region of union. 

It is more difficult to unite pieces of different species of worms, 
yet Joest has succeeded also in making combinations of this sort. 
One union between the anterior end of Lutnbricus rubellus and the 
posterior end of Allolobophora tcrrestris was permanent, and the new 
worm reacted as a single individual, and lived for eight months. 
Each piece retained its specific characters, and showed no influence 

^ See Joest's Fig. 14. 

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GRAFTING AND REGENERATION 



173 



of the other component. By means of a similar experiment we have 
a way of finding out if one component can influence regeneration 
taking place from the other piece. Although Joest made only a few 
observations of this sort, the results show that no such influence is 
manifested. 

By means of grafting it is possible to keep alive small pieces of a 
worm that would otherwise perish. For instance, pieces of a worm 







Fig. 53. — After Toest. A. Small piece of Allolohaphora terrestris from posterior end grafted upon 
anterior end of another individual. Oral end free. Four weeks after grafting eight new 
segments formed. B. Same fourteen days later. A 'new part of thirty-seven segments had 
appeared at end of former eight segments. C A piece of the body wall of Alhlobophora 
terrestris grafted upon the cut-end (anterior) of LumbrUus rubellus. Two months later, as 
shown in figure, a head had grown on major component. D, Anterior and posterior ends of 
A. terrestris united to make a " short worm." E. A piece of body wall of A, cyanea grafted 
on side of body of Lumbricus rubellus. F. Piece of L. rubellus grafted on side of body of 
another individual to produce a double-tailed worm. 

containing only three segments are not capable of independent exist- 
ence, except for a short time, and even pieces of from four to eight 
segments die in most cases. It is not possible to unite small pieces 
of this size directly upon larger pieces, since they will die, ordi- 
narily, as a result of the operation, but larger pieces can be united 
and then after union has been effected, one of them may be cut off 
near the place of union. The same result is sometimes^brought 

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174 REGENERATION 

about accidentally by the worms themselves pulling apart and leav- 
ing a small piece of one component attached to the other. Joest 
found that in several cases these small, attached pieces regenerated. 
In one case, after two long pieces had pulled apart, a small piece, left 
by one of the two, regenerated a single new segment with a mouth at 
its end. In another case, after one of the components had been cut 
off, leaving two segments attached, a new part of seven segments 
regenerated.^ Especially interesting is the case in which two indi- 
viduals (A. terrestris) had been united to form a long worm. The 
anterior component extended to within two centimetres of the anus; 
the posterior piece had had the first four segments removed. Three 
days later the anterior piece was cut off three segments in front of 
the region of union. About a month later a small part of eight seg- 
ments had regenerated from the cut-end (Fig. 53, A\ Fifteen days 
later another new part of thirty-seven segments developed at the end 
of the first new part (Fig. 53, B\ Joest speaks of the first eight seg- 
ments as a head, and the second simply as a regenerative product. 
There can be little doubt, I think, that both parts represent a hetero- 
morphic tail. The region from which the regeneration took place 
would make this interpretation highly probable, and Joest's figures 
also indicate that the structure is a tail. The result is very interest- 
ing, if my interpretation is correct, as it shows that the major com- 
ponent did not influence the kind of regeneration, although the 
surface of regeneration was separated by only three tail-segments 
from the anterior end of the major component. 

In another experiment a long animal was made by uniting Lum- 
briais rubellus (whose posterior third had been cut off) and Allola- 
bophora terrestris (whose first six segments had been cut off). Four 
days later the two components had torn apart, but a small piece of 
the anterior worm remained attached to the anterior end of the pos- 
terior component. The small piece consisted of the dorsal part of 
two and a half segments without any ventral part, so that the anterior 
end of the posterior component was partially exposed. The small 
piece of lumbricus was much lighter in color, and this difference 
made it easy to distinguish between the two. In less than a month 
the small transplanted piece had replaced its missing ventral part, so 
that the entire anterior surface of the larger component was covered 
over. The small piece, in addition to regenerating its ventral part 
of four segments, had also begun to make new segments. After a 
month and a half six new segments were present (Fig. 52, E\ with 
a mouth at the anterior end.^ Even adter ten months the color of 

^ It is not certain whether this is a head or a tail. 

^ Joest states that this new part is a head, as shown by the presence of food matter in the 
digestive tract of the posterior piece. 

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GRAFTING AND REGENERATION * 1 75 

the small piece was strikingly different from that of the major com- 
ponent. The new head had the typical red-brown color of Z. rubelluSy 
that forms a strong contrast to the grayish blue color of A, terrestris} 
The result shows that the color of the regenerated part has not been 
influenced by that of the posterior component, and this is all the more 
interesting, as Joest points out, because the small piece that ^as left 
after the worms pulled apart was too small to have lived independently 
for any length of time, and must have derived all its nourishment 
from the larger piece. 

In other experiments pieces of one species were cut from the side 
of the body and grafted upon the cut-surface of the anterior end (or 
elsewhere) of another species. In one of these experiments a piece 
from the side of A, terrestris, that extended over five or six segments, 
was sewed upon the anterior cut-surface of Z. rubellus (from which 
the anterior five segments had been removed). In about a month new 
tissue appeared on the ventral side between the two pieces, and a 
little later a complete head developed, whose dorsal side was made up 
of the small piece (Fig. 53, C). The grafted piece was dark, and the 
new, regenerated part light in color and continuous with the brown 
color of L. rubellus, from which the new part had arisen. It is 
important to notice that the four segments of the graft are completed 
by four segments of the new part. After three months the new part 
had assumed the red-brown color of L, rtibellus. The color of the 
grafted piece had not changed. We see in this case that even the 
presence of a part of another worm in a regenerating region does not 
have any influence, at least so far as color is concerned, on the new 
part, even though its segments supplement some of those of the 
new part. The new tissue seems to have come entirely from the 
major component, and to have carried over the color characteristics 
of the old part. 

It has been shown that when two posterior pieces are united by 
their anterior ends the combination must sooner or later die, since it 
has no way of procuring food. The question arises : What will hap- 
pen if one of the two components is cut in two near the place of 
union.? Will a head then develop on the exposed aboral surface, 
because a head is needed to adapt the worm to its surroundings, or 
possibly, if it occurred, because the major component exerts some 
sort of influence on the short, attached piece, as happens in hydra 
and in tubularia.? Both Joest and I carried out an experiment 
of this sort, and found that a tail and not a head regenerated, as 
shown in Fig. 16, F, The experiment is, however, insufficient to 
answer the question, since the region in which the second cut was 
made is a region from which only a tail (and not a head) arises, even 

1 The prostomium was misshapen, so that its specific character could not be made out. 

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1 76 REGENERA TION 

when the oral end of a piece is exposed. In order to avoid this diffi- 
culty I carried out another experiment. Two worms had the first 
five or six segments cut off and the exposed anterior ends of the 
worms united, as shown in Fig. 16, D. Then one of the components 
was cut off, leaving three or four segments attached to the anterior end 
of the other component. Although regeneration began in one case, it 
did not go far enough to show what sort of a structure had developed, 
but Hazen, who took up the same experiment, succeeded in one case 
in obtaining a definite result. At the exposed aboral end of the 
small piece a head and not a tail developed (Fig. 16, E\ At first 
sight it may appear that the result shows the influence of the major 
component on the small piece, causing it to produce a head and not a 
tail at its aboral end, but I think that this conclusion would be 
erroneous, because it seems much more probable that we have here a 
case of heteromorphosis, similar to that in Planaria lugubris, and that 
the result depends entirely on the action of the smaller component. 
It is hardly possible to demonstrate that this is the correct interpre- 
tation, since if a small piece of this size is isolated it dies before it 
regenerates. The result is paralleled, however, by the regeneration 
of a tail at the anterior surface of a posterior piece. 

The process of grafting has long been practised with plants, but 
the experiments were made more for practical purposes than to study 
the theoretical problems involved. Vochting has, however, carried out 
a large number of well-planned experiments. He finds that a stem 
can be grafted upon a root, and a root upon a stem, a leaf upon 
a stem or upon a root. Even an entire plant can be grafted upon 
another. The results show, however, in general, that, whatever the 
new position may be, the graft retains its morphological characters — 
a shoot remains a shoot, a root is always a root, and a leaf a leaf. 
Vochting concludes that there is in the plant no principle or organi- 
zation that conditions an unchangeable arrangement of the main 
organs. " The inherited order of the parts, acquired apparently on 
physiological grounds, may be altered by the experimentator ; it is 
possible for him to change the position of the building blocks within a 
wide range without endangering the life of the whole." " It is essen- 
tial, however, for the success of the experiment that the grafted 
parts, or tissues, retain their normal orientation. If this condition is 
not fulfilled there may take place, it is true, a union of the parts, but 
sooner or later disturbances set in." Vochting transplanted pieces in 
abnormal positions, sometimes reversing the long axis of the grafted 
piece, sometimes the radial axes, and sometimes both together. In 
some cases this led to the formation of swellings that interfered with 
the nourishment but carried with it no further consequences. In 
other cases the changes went so far that the vital processes were inter- 



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GRAFTING AND REGENERATION ly/ 

f ered with. At times an incomplete union took place between the 
parts ; at others, even though the first union was perfect, death later 
ensued. 

On the other hand, when similar pieces were grafted with their 
original orientation, a perfect union took place and the piece became 
a part of the stock. The results establish, Vochting claims, that 
every part and every portion of a part has a polar orientation in one 
direction, and furthermore, in a body having a radially symmetrical 
form, there is also a radial polarization; that is, the inner side of 
each part is different from the outer side of the same surface, even 
though no such difference is apparent to us. The properties of the 
tissue-complex rest, in the last analysis, on that of the cells ; the 
properties of the whole being only the sum total of the properties of 
its elements, so that we may say that every living cell of the root 
is polarized, not only longitudinally, but also radially; each has a 
different apical and root pole, a different anterior and posterior pole, 
and also right and left polar relations. These results, deduced from 
the experiments in grafting, lead Vochting to formulate the follow- 
ing rule : ** Like poles repel, unlike poles attract." This rule is the 
same as the law of the magnet. In fact, Vochting states that the 
root and the stem relations show a remarkable resemblance, despite 
many differences, to a magnet. If the magnet is broken into pieces 
it may be reunited by bringing unlike poles together, but not by unit- 
ing like poles ; the same statement holds for the root and the stem. 

Exception may be taken, I believe, to parts of Vochting's conclu- 
sions, especially in the light of the recent experiments in grafting in 
animals. It is by no means to be granted without further demonstra- 
tion that the properties of the whole organism are only the sum- 
total of the action of the individual cells. If, as seems to be the case, 
the cells are organically united into a whole, the properties of this 
whole may be very different from the sum of the properties of the 
individual cells, just as the properties of sugar are entirely different 
from the sum of the properties of carbon, hydrogen, and oxygen. 

The statement that like poles repel and unlike poles attract is, I 
believe, a conclusion that goes beyond the evidence. The experi- 
ments show that like poles do often unite in plants, and this has 
been abundantly shown to be the case in the lower animals, and even 
in forms as high as the earthworm and the tadpole. Even if when like 
poles are united subsequent changes take place, that in some cases, 
although apparently not in animals, lead to the death of the graft, it 
by no means follows that this has anything to do with the attraction 
or repulsion of the parts, but rather with some difficulty in obtaining 
food, or with the transportation of substances through the plant. In 
the lower animals we have seen that when like poles are united 



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1 78 REGENERA TION 

there is sometimes a stronger tendency to produce new organs at or 
near the place of union than when unlike poles are united, but it 
would be going too far, I think, to state that this is due to repulsion 
of the parts, especially in the sense in which the like poles of a 
magnet repel each other. It seems to be due rather to the two parts 
failing to unite into a whole organization, each retaining the same 
structural basis that it had before grafting, but this is a very different 
principle from that of an attraction and repulsion of the parts, and 
the question of the union of the parts appears also to be a different 
question from that of the organization of the parts themselves. 

In the mammals, and in general in all forms in which there is a 
dependence of the parts on each other, it is impossible to carry out 
grafting-experiments on the same scale as those described in the pre- 
ceding pages. The principal difficulties are to make the parts unite, 
and to supply nourishment and oxygen to the graft Owing to the 
dependence of the parts of the body on each other for a constant sup- 
ply of oxygen and food derived from the blood, as well as for the 
removal of the waste products, the parts cannot remain alive, or even 
in good condition, while new connections are being established. For 
this reason, as well as for others, it would not be possible, for instance, 
to graft the arm of a man upon another man. The tissue may have the 
power of uniting even in this case, as is seen when the bone is broken 
and subsequently reunited, but the difficulty would be in supplying the 
grafted arm with nourishment, etc., during the long time required for 
the union to take place. Smaller parts of the body may be success- 
fully grafted, and there are several recorded cases in which parts of a 
finger, or of the nose, are said to have been cut off and to have reunited 
after being quickly put back in place. Pieces of human skin may be 
grafted without great difficulty upon an exposed surface, and it has 
been said that small pieces succeed better than larger ones, owing, 
most probably, to their being able to absorb sufficient oxygen, etc., and 
keep alive until new blood vessels have grown into the grafted piece. 

There are a number of old and curious observations in regard to 
cases of grafting in higher animals. It was found by Hunter and by 
Duhamel that the spur of a young cock could be grafted upon the 
comb, when it continued to grow to its normal size. The comb, being 
richly supplied with blood, furnished the nourishment for the growth 
of the spur. Fischer transplanted the leg of an embryo bird to the 
comb of a cock, or of a hen, where it grew at first, but after some 
months degenerated. Zahn transplanted the foetal femur to the kid- 
ney, where it grew for a time, but later degenerated. Bert transplanted 
the tail of a white rat to the body of Mus decumanus, where it continued 
alive ; but he found that the tail of the field mouse, Mus syivaticiis, 
did not grow so well on the rat, and the tail of a rat would not unite 



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GRAFTING AND REGENERATION I'/g 

at all with the body of a dog or of a cat. Bert bent over the tip of 
the tail of a rat, and grafted the distal end into the skin of the back 
of the same animal. After the tip had established union with the 
surrounding tissues, the tail was cut off at its base. The grafted tail 
remained alive, but did not regenerate at its free end. 

There are several cases described by pathologists in which the skin 
of one mammal has been transplanted to another. The transplanta- 
tion of the skin of the negro upon a white man has been brought 
about, but the evidence as to what subsequently happened is contradic- 
tory. It appears that while in many instances the transplanted skin 
has remained alive for a time, yet later it was thrown off by new skin 
growing under it and replacing it. 

Leo Loeb has described a curious instance of grafting pieces of 
skin of different colors in the guinea pig. If a piece of black skin 
from the ear of a guinea pig is grafted upon the white ear of another 
animal, it unites and continues to live, but if a piece of white skin is 
grafted upon a black ear, it is slowly thrown 'off and replaced by 
new black skin that has regenerated around the edge of the graft from 
the tissue of the black ear. 

In the literature of pathology there are many cases described in 
which parts of the body of mammals, particularly internal organs, 
have been grafted in unusual regions. The results have not 
always been the same, for while in some cases it appears that the 
operation has succeeded, in others the grafted part is subsequently 
absorbed, and in still other cases the graft may be at first partly 
absorbed and later begin to grow again. It appears that the estab- 
lishment of an adequate blood supply is the most important element 
of success. Ribbert, who has made an extensive and successful series 
of experiments, has stated that the grafting takes place better when 
small pieces of an organ are used, since these can draw immediately on 
the surrounding regions for their oxygen, etc., while larger pieces are 
found to break down in the interior, owing to the fact that this part is 
too far removed from the supply of oxygen, food, etc. After the grafted 
piece has established a blood supply of its own, it may continue to 
grow. Ribbert transplanted small pieces of different tissues of the 
rabbit and guinea pig in, and upon the surface of, the lymph glands 
of the same or of another individual. The lymph gland was chosen 
because small pieces of tissue can be afterwards easily detected. A 
small piece of tissue about as large as a pin's head is cut off from 
whatever tissue is to be grafted, and as quickly as possible placed in 
a small cleft made in the lymph gland. After several days, weeks, or 
months, the gland is removed and the graft examined by means of 
serial sections. 

Most of the experiments were made with " epithelial organs," and 

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l80 REGENERATION 

according to Ribbert, if pieces of such organs are composed of 
epithelium only, they cannot be successfully grafted. For instance, 
the cells of the cornea can be readily separated from their under- 
lying connective tissue, and can be kept alive in the lymph gland, 
but the cells diminish in number, show retrogressive metamorphosis 
in the direction of atrophy, and are finally absorbed. It seems that 
epithelium by itself cannot extract nourishment from its surround- 
ings. Nothing is easier, however, than to transplant epithelium, 
if its connective tissue is present. The connective tissue furnishes 
so good a basis for nourishment that the epithelium not only lives, 
but may continue to proliferate. Ribbert finds that pieces of skin 
roll in after their removal. Then a process of growth takes place 
corresponding to that which follows a wound in the skin. The 
surface is closed and a small cyst is formed with a central cavity. 
The epithelium undergoes no changes during the first days or weeks. 
It remains stratified and shows an active process of cornification and 
desquamation. Similar results were obtained when pieces of the 
conjunctiva were transplanted, either under the skin in the anterior 
chamber of the eye, or in the lymph gland. 

A small piece of the lining epithelium of the trachea with its 
underlying cartilage was also placed in the lymph gland. The epi- 
thelium grew, and covered over the wounded surface, forming over it 
only a single layer of cells. The old many-layered epithelium also 
became arranged in a single layer. 

The wax glands, found in the inguinal folds of the rabbit, were 
also transplanted. The gland is composed of closed, compressed 
alveoli, surrounded by large, polygonal, clear cells. Small pieces of 
a gland, transplanted upon the lymph gland, underwent character- 
istic changes. The cells of the alveoli were changed into a stratified 
epithelium ; and broken-down cells, and wax, were found in the interior 
of the alveoli. The central alveoli underwent the greatest change, 
while some of the peripheral alveoli that were in contact with the 
lymph gland remained unchanged. It seems that the difference is due 
to the better nourishment of the outer alveoli. After several months 
the alveoli swell up and degenerate. Transplanted pieces of the 
salivary glands also change, the alveoli producing a lining epithelium 
like that of the transplanted wax gland. The same change was ob- 
served in a piece of a salivary gland transplanted in the body cavity. 

Small pieces of the liver were cut off and placed in the lymph 
gland. They did not always grow as well as did the preceding 
tissues, but often went to pieces. If they healed, the liver tissue 
often remained unchanged for several weeks. After two or three 
weeks connective tissue appeared between the peripheral liver cells, 
separating the cells from each other. The cells grew smaller, their 



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GRAFTING AND REGENERATION l8l 

protoplasm disappeared, and they at last disintegrated. Pieces of 
the gall duct behaved differently. They sometimes showed active 
growth, leading to the development of numerous branched canals.^ 

Pieces of the kidney, when transplanted, suffered a great change, 
and were subsequently absorbed. Transplanted pieces of a testis 
also changed. After six days, Sertoli's cells and the spermatozoa 
disappeared. A kind of indifferent cell remained, characterized by 
clear protoplasm and by a large nucleus. After seventeen days 
further changes were observed, and later the pieces were com- 
pletely absorbed. Pieces of the ovary rapidly disappeared, leaving 
only a mass of interstitial connective tissue. 

The connective tissue underwent, in all the transplanted pieces, 
characteristic changes. The tissue became less dense, the protoplasm 
and nucleus of each cell enlarged. The cells multiplied, but only 
very slowly. These changes took place after one or two days. After 
a month or two the cells became more compact, their processes more 
numerous, and the nucleus small and long. Later degeneration set in. 

Small pieces of bone from the caudal vertebrae were also trans- 
planted, care being taken that each piece should contain some of the 
periosteum and marrow. The bone tissue goes to pieces, but the 
periosteum and marrow develop further. New bone is formed from 
the cells of the marrow as well as from those of the periosteum. 
Finally the entire piece, both its old and its new parts, is absorbed. 
Pieces of muscles were also absorbed. 

These experiments of Ribbert show that transplanted pieces of 
tissue do not increase in size by growth, but undergo changes 
which he describes as a return to an earlier condition of develop- 
ment. The abnormal condition of their existence seems to be the 
cause of this change. The transformation may be due to a change 
of nourishment, or to a loss of nerve influence, or to lessened func- 
tional activity. 

These results have a direct bearing on the problem of regenera- 
tion. They show that all kinds of tissue may continue to live, and 
the cells multiply in different parts of the body, but there seems to 
be nothing in these cases comparable to a regeneration of the entire 
organ. In the new situation the cells often assume an entirely new 
arrangement. After a period of activity, a process of degeneration 
commences, and the piece atrophies. Ribbert thinks that the atrophy 
is due to lack of nourishment, yet it is not clear how this could be 
the case, since for the first few weeks after transplantation there is 
an active growth, and in some cases, as in that of the bone, there is a 
formation of new, characteristic tissue. It may be that the trans- 

* It is known that the process of regeneration of the liver takes place especially from 
the gall ducts. ^^ . 

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1 82 REGENERA TION 

planted tissues can no longer manufacture the substances necessary 
for their specific growth, and after the materials that have been 
brought along with them have been used up, the growth of the piece 
is stopped and its subsequent degeneration begins. It would be 
interesting to see if pieces transplanted to the same kind of organ 
as that to which they belong will become permanently incorporated 
in their new position. 

y The grafting-experiments that have been described in the preced- 
ing pages were carried out with pieces of adult organisms. Some- 
what different conditions are present when parts of the developing 
egg or embryo are united, inasmuch as a process has been started 
in them that may go on independently, to a certain extent, of the union 
of the pieces. Born has carried out a large number of experiments 
in grafting parts of tadpoles of the same species, and also of differ- 
ent species. The union is brought about at the time when the tad- 
poles are about to leave the jelly membranes. The cut-surfaces are 
brought in contact and the pieces pushed together and held in place 
for an hour or two by means of small silver blocks or pieces of wire. 
The pieces readily stick together, and the union is a permanent one. 
Before describing Born's results, it may be well to consider the power 
of regeneration of young tadpoles. If the tail is cut off a new one is 
regenerated by the tadpole, but all parts of the body do not have 
this same power. Schaper found that if a part of the brain, or even 
the entire brain, is removed, no regeneration takes place. I have 
found that if the region where the heart is about to develop is cut 
out from a young embryo, a new heart is not formed.^ If a tadpole 
is cut in two across the middle of the body, neither piece regenerates 
the missing half. Byrnes has found, however, that if the region from 
which the posterior limb develops is cut out a new limb regenerates. 
In older tadpoles, Spallanzani found that if the hind limb is cut off 
it will regenerate, and Barfurth has more recently confirmed this 
result. The end of the tail that has been cut off from a young tad- 
pole, before the tail has begun to differentiate, may continue alive for 
several days. It grows larger and flatter, and the V-shaped meso- 
blastic somites are formed. A slight regeneration even starts at its 
anterior end, as first observed by Vulpian and later by Born. The 
notochord and nerve-cord may send new tissue into the new part, and 
even some of the muscle cells may extend into this part, but the piece 
dies -before regeneration goes any further. If, however, the tail is 
grafted in a reverse direction on the body of another tadpole, the 
regeneration may go further and produce a tail-like structure, as 
Harrison discovered and as I have also seen. 

^ In one case I observed rhythmic pulsations in a vessel on one side of the neck, in the 
region above the pharynx. 

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GRAFTING AND REGENERATION 1 83 

Bom found that if the anterior half of one tadpole was united to the 
posterior half of the same or of another tadpole a single individual was 
formed which he kept alive in several cases until the time of metamor- 
phosis. If the head of a tadpole is cut off and grafted upon the side 
of the body of another tadpole, the head will remain alive and con- 
tinue to develop in its new position, and, if well nourished by means 
of the connecting blood vessels that develop, it may grow to be as 
large as the head of the tadpole to which it is attached. Similarly, if 
the tail of one tadpole is grafted upon the side of the body of another 
tadpole, it also continues to develop, and at the time of metamorphosis, 
when the normal tail is absorbed, the additional or misplaced tail also 
shows signs of breaking down. Even the posterior half of one tad- 
pole, if grafted to the ventral side of another, may continue to develop, 
producing legs, etc. 

Born succeeded in uniting tadpoles of different species in several 
different ways. They were united by their heads or by their ventral 
surfaces, or longer and shorter tadpoles made by using pieces longer 
or shorter than a half. In all of these cases there is no regeneration 
at the place of union, and the internal organ, the digestive tract, ner- 
vous system, and blood vessels unite when brought into contact. 
When pieces are united end to end, like organs unite to like, the 
nerve-cord with the nerve-cord, digestive tract with digestive tract,, 
segmental duct with segmental duct, coelom with coelom, and although 
less often, the notochords sometimes join together. The lack of 
union of the ends of the notochord is explained by its frequent par- 
tial displacement at the cut-end, for when the cut is made the noto- 
chord, being tougher than the other structures, is often dragged out of 
place in one or in both pieces, so that the ends do not meet when the 
pieces are put together. When like organs are brought together the 
substance of one unites directly with the substance of the other, and 
if the organ is a hollow one, as is the digestive tract or the nerve-cord, 
their cavities also become continuous. There is also, Born states, 
some evidence to show that if similar organs are not brought exactly 
in contact their ends find each other and unite, and if they do not at 
first meet squarely they may do so later. When the ends of unlike 
organs are brought in contact, as, for instance, the nerve-cord and 
notochord, they do not unite, but connective tissue develops between 
them. The union of like parts, Born suggests, may be due to some 
sort of cytotropism, the outcome of a mutual attraction between simi- 
lar cells like that which Roux has observed between the isolated 
cells of the segmented ^g^ of the frog. Born thinks that the first 
rapid union of the pieces is due to the attraction of the ectoderm of 
one component for that of the other. 

Bom succeeded also in uniting pieces of the tadpoles of JifTerent 

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1 84 



REGENERATION 



species, even when they belonged to different genera. It is found, 
however, that some of these combinations can be more easily made 
than others, but it is not clear whether the difference depends upon 
differences in the sizes of the pieces, or the rate of growth of the ecto- 



(^^^ 




Fig. 54. — A, After Harrison. Union of two tadpoles by posterior ends. Two days after opera- 
tion. The line to the left of plane of union indicates where the two were cut ai>art. B. Tail 
of right-hand tadpole in A. Five days after cutting apart. C. Same. Nine days after cut- 
ting apart. D. Same. Ninety-five days after cutting apart. E, After Born. Combination 
of Rana escuUnta (anterior) and Rana arvalis (posterior) . Thirteen days after the operation. 

derm over the cut-surfaces, or to a deeper-lying lack of affinity between 
the tissues. A combination of Rana esculenta (anterior) with Bombi- 
nator igneus (posterior) was made. The combination lived for ten 
days, and then showing pathological changes, it was killed. Another 
combination is shown in Fig. 54, E, in which the anterior part of Rana 

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GRAFTING AND REGENERATION 1 85 

escttlenta was united to the posterior part of Rana arvalis} The blood 
of the posterior component was driven through the vessels by the 
action of the heart of the anterior component. The animal lived 
for seventeen days. 

In all these combinations between different species, each develop- 
ing part retains its specific characters, and, although in several cases 
one part received its nourishment from the other through the com- 
mon circulation, yet no influence of one component on the other 
could be observed. 

Harrison has succeeded in keeping an individual made up of two 
species, Rana virescens and Rana palustris^ for a much longer time, — 
until, in fact, the transformation of a tadpole into a frog had taken 
place. Each half retained the characteristic features of the species 
to which it belongs. • 

The absence of regeneration after the union of the pieces may 
Ije attributed, in several cases, to the absence of this power in the 
region through which the cut has been made ; but in other experiments 
this cannot be the explanation, since the power to regenerate can be 
shown to exist in the part. This is the case in an experiment car- 
ried out by Harrison and repeated later by myself. If the tips of 
the tail of two tadpoles are cut off and interchanged (Fig. 55, A, B\ 
a perfect union takes place between the two parts, and a single tail 
develops. Each of the cut-surfaces has the power to regenerate, 
but the union of the parts has suppressed the regeneration. If, 
however, like parts are not brought in contact, regeneration may take 
place in the region of union (Fig. 55, D\ 

Both Harrison and I have made a number of experiments, in 
which the end of the tail of a tadpole of one species was inter- 
changed with a similar part of another species. It is found that as 
the new tail grows larger the ectoderm of the grafted piece is car- 
ried out to the tip of the new tail, as shown in Fig. 55, C, and does 
not cover all the inner tissues that belong to the same piece, the 
rest of the tail being covered by the ectoderm of the major com- 
ponent. If the tip of the tail is now cut off, as indicated by the line 
Ih-b in Fig. 55, C, there are left at the exposed edge two kinds of ecto- 
derm, and from the cut-edge a new tail regenerates, covered in part 
by each of the two kinds of ectoderm. I made this experiment in 
order to see if the new ectoderm would show any influence of its 
dual origin, especially along the line where the two kinds are in con- 
tact, but no influence could be detected. In another series of experi- 
ments the grafted tail was cut off, as shown in Fig. 55, A, or in Fig. 
55, jff, or in Fig. 55, C, a-^a. In these cases there is left exposed, at 
the cut-edge, the internal tissues of the two species. The new tail 

1 The figure was drawn fifteen days after union. 

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186 



REGENERA TION 



that regenerates is composed in part of material derived from one 
species and in part fronl that of the other, but each tissue remains 
true to its kind, and there is found no evidence of an influence of one 
on the other (Fig. 55, E), These experiments show that even when 
the two kinds of tissue regenerate side by side, and unite to form a 
single morphological organ, there is no influence of a specific kind 
of one tissue on the other. 





B 






Fig. 55.-— /I. Rana syhatica with grafted tail of R ana patmtris. Line a-a indicates where tail 
was cut oflf. Z?. Rana palusiris with grafted tail of Rana sylvatica. Line a-a indicates where 
tail was cut off. C. Older stage of a graft like B. Lines indicating two possible operations. 
D. Another individual with two tails, one composed of both components. E» Later stage of 
last, when tail was cut off at level a-a. 

Another series of experiments in grafting, similar to one of those 
made by Joest and myself on the earthworm, has been made by Har- 
rison on the tadpole. I have also later made similar experiments. 
Two tadpoles are united by their posterior ends, as shown in Fig. 54, A, 
and a day or two after union one of the tails is cut off near the line 
of union. There is thus left attached to the end of the tail of one 
tadpole a part of the tail of the other united in a reverse direction, so 
that the exposed cut-end is the anterior end of the small piece. 
There grows out from this cut-end a structure that resembles a tail 
(Fig. 54, B, C, D\ It contains a continuation of the notochord and 
nerve-cord, that taper in a characteristic way to the end of the new 
structure. The tail is flat and has a central band of muscle tissue, and 

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GRAFTING AND REGENERATION 18/ 

a dorsal and ventral fin* The muscles of the normal tail have a 
characteristic V-shaped arrangement with the apex of the V's turned 
forward, but unfortunately in the new tail the muscles are so 
irregular that it is impossible to make out their arrangement 
(Fig. 54, D), If the new part is in reality a tail, the V's ought 
to stand in the same way as do those in the major component, and 
opposed to the V's on the part from which the new material arises. 
If the new structure is not a tail at all, but a new growth, or even a 
suppressed trunk, then the V*s should stand as in the small part itself. 
It has not been possible as yet to obtain a decisive case. Harrison 
obtained one case in which the arrangement of the muscles in the 
new part seemed to be more as it should appear if the new part is 
a heteromorphic tail (Fig. 54, D\ Even if this could be shown to be 
the case, it may be that under the conditions of the experiment the 
arrangement of the muscles is determined by the use of the tail, 
although this does not seem very probable. Harrison, after a careful 
analysis of the question, left it undecided, but seemed more inclined 
to the view that the result is due to the development of something 
new rather than a heteromorphic growth. On the contrary I am 
strongly inclined to believe that the latter is the true explanation. In 
another way I have been able to bring about the development of the 
same structure. A small triangular piece is cut from the upper part 
of the tail, as indicated in Fig. 56, A, one point of the triangle passing 
through the notochord, or even through the aorta. If the cut-surfaces 
are kept apart for a few hours, until the exposed end has been covered 
over by ectoderm, they may not unite afterward, and two exposed 
surfaces are left, — one at the distal end of the base of the tail, and the 
other at the proximal end of the outer part of the tail. The latter 
surface corresponds to that in the grafting-experiment. Regenera- 
tion may take place from the two surfaces ; both new parts seem to 
be exactly alike, and both resemble a regenerated tail. The one from 
the proximal surface of the outer part of the tail contains a notochord, 
nerve-cord, connective tissue, pigment cells, and muscle tissue (Fig. 56, 
B\ The arrangement of the muscle fibres is generally very irregular, 
and the characteristic V-shaped arrangement cannot be detected. 

In only a few cases have attempts been made to unite two eggs 
or two very early embryos, although there are a few casual observa- 
tions ^ in which such a fusion has been observed. The problems that 
arise in connection with the union of two eggs are full of interest. 
Each egg has the power of producing an embryo of normal size. If 
two eggs are united into one, will a single giant organism result, or 
two organisms t If the former, we must suppose that a new organi- 
zation is formed of double size. Whether an upper limit of organiza- 

1 Metschnikof! ('86), Herbst ('92). ^ , 

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1 88 



REGENERATION 



tion exists can only be determined by such an experiment. If two 
fused organisms result from the fusion of two eggs, it would show 
the structure of the egg is of such a kind that two organizations can- 
not readjust themselves into a single one of double size. Moreover, it 
is important to discover whether any difference exists as to the stage 
of development at which the union is brought about, for it is conceiv- 
able that while a rearrangement is possible at one stage, it might 
not be at another. 





Fig. 56. — A, Tadpole to show where the V-shaped piece is cut from the tail. B, Later stage of 
same with a new tail-like outgrowth from the anterior end of tail. 

It has been shown that two blastulae of the sea-urchin can be 
united to form a single embryo. I found ('95) that occasionally two 
blastulae stick together and fuse, so that a single sphere of double 
size is formed. As a rule two gastrulae and two more or less com- 
plete embryos develop from each double blastula, but in a few cases 
I found that a single embryo may be formed, that shows, however, 
traces of its double origin. Driesch has more recently (1900) suc- 
ceeded ^ in bringing about more readily a union of two segmenting 

^ Eggs without membranes were placed in sea water without calcium, to which a few 
drops of sodium hydroxide have been added. 

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GRAFTING AND REGENERATION 1 89 

eggs or blastulae, and obtained perfect single individuals from two 
fused blastulae. He finds that if the fusion takes place at an early 
stage the resulting embryo is less likely to show its double origin 
than when older blastula stages are united. Zur Strassen has also 
observed giant embryos of ascaris that arise by a fusion of two eggs. 
Loeb has found that the eggs of chaetopterus, which can be made to 
develop parthenogenetically in certain salt solutions, often stick to- 
gether and produce giant embryos. 



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CHAPTER X 
THE ORIGIN OF NEW CELLS AND TISSUES 

There are many difficulties in the way of determining the origin 
of the cells that make up the new part. The only means at present 
at our command for studying their source is by serial sections of a 
number of different stages taken at intervals from different animals. 
Since there may be differences between the processes in different in- 
dividuals, and since we can only piece together the information gained 
from successive stages, much uncertainty exists in regard to the 
changes that take place during regeneration, even in some of those 
forms that have been examined over and over again. Were it possi- 
ble actually to follow out the movements of the living cells in one and 
the same animal, the problem would offer fewer difficulties, but this 
cannot be done. It will be more profitable to consider first the bet- 
ter-known and simpler processes, and afterward those that are less 
well-known. 

The regeneration of the head and tail of lumbriculus and of cer- 
tain naids is a comparatively simple process, and has been studied by 
several investigators, whose results agree, at least in regard to the most 
essential features. Semper ('76) described the origin of the new 
organs in the formation of new individuals by budding in nais. He 
found that the new brain and nerve-cord develop from the ectoderm, 
the new mesoderm also from ectoderm, and the new digestive tract from 
the old one, except the pharynx, which arises by the fusion of two meso- 
dermal " gill-slits." Billow ('83) studied the regeneration of the tail of 
lumbriculus. He found the ventral cord in the new part arising from a 
paired ectodermal thickening, the mesoderm arising from a prolifera- 
tion of cells. These cells are invaginated in the region between ecto- 
derm and endoderm — the in-turning of the proctodaeum being looked 
upon as an endodermal invagination.^ The more recent work of Ran- 
dolph, Rievel, Michel, Hasse, Hepke, and von Wagner on the same or 
related forms has served to point out certain errors in the earlier work 
of Semper and Billow, and has added some new and important facts, 
especially in connection with the origin of the mesoderm in the new 
part. Without attempting to give a detailed account of these results, 

' The usual interpretation at present is to regard the proctodaeal ingrowth as ectodermal. 

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THE ORIGIN OF NEW CELLS AND TISSUES 



191 



I shall describe the principal changes that have been found to take 
place. When the anterior end of lumbriculus or of tubifex is cut off, 
the cut-surface very quickly closes, as a result of the contraction of 
the body wall. According to some investigators, the circular muscles 
are chiefly concerned in the closing, but according to others the lon- 
gitudinal muscles bring about the result. The cut-end of the diges- 




Fig. 57. — After Hasse. Regeneration of head ol Tubifex rivulorum. A, Sagittal section of an- 
terior end. Six days afier cutting in two. B. Eleven days after cutting in two. C. Cross- 
section through new part Five days after operation. D, Fourteen days after operation. 
E, Sixteen days after operation. 

tive tract is pulled a little inward, and its end also closes (Fig. 57» ^)- 
For a day or two no important changes can be observed to take 
place, but new ectoderm soon appears over the cut-surface. This ecto- 
derm arises in all cases from the old ectoderm, and as it increases in 
amount the old ectoderm is pushed back from over the cut-end, leav- 
ing a layer composed of a single row of cells over the end. Since 
nuclei in process of division are rarely present before these initial 

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192 REGENERATION 

processes begin, it is probable that the changes are due, in large part, 
to an out-wandering of ectodermal cells, or, what amounts to the same 
thing, to the leaving behind of cells as the old ectoderm withdraws from 
the cut-end. In the new ectoderm over the end, an active process of 
proliferation takes place (Fig. 57, B\ that leads to the production of a 
large number of cells lying within the new part. The ectoderm has at 
this time begun to bulge outward, so that the proliferated cells come 
to lie within the dome-shaped beginning of the new head. There 
appears to be some difference in the number and in the location of 
the proliferations in different species. In general, the new cells arise 
from the ventral and ventro-anterior region of the dome-shaped ecto- 
dermal covering of the new part. Most of this new material gives 
rise to the brain, commissures, and ventral nerve-cord (Fig. 57, Q. 
The cells giving rise to these structures in tubifex come from two ven- 
tral regions of proliferation that extend along the sides and dorsally to 
the anterior end in front of the digestive tract. Where the two masses 
meet above and in front, the brain is formed.^ The cells that do not 
take part in the formation of the nervous system give rise to the mus- 
cles and connective tissue of the new head. These cells lie especially 
at the outer sides of the proliferated mass. The origin of the new 
muscles from ectoderm stands in sharp contrast to the current ideas 
in regard to the origin of new tissues, and yet it is a point on which 
the more recent investigators are entirely in accord. Michel, Hepke, 
and von Wagner have arrived at the same conclusion after a careful 
examination, and there seems to be no reason for refusing to accept 
their results. The theoretical importance of this discovery will be 
discussed later. 

Soon after the proliferation from the ectoderm has begun, the 
blind end of the digestive tract starts to push forward (Fig. 57, D). 
The cells in the most anterior part of its wall begin to divide, and the 
end grows in an anterior direction as a more or less solid rod. This 
rod extends, in some species, as far forward as the ectoderm, meeting 
the latter on the inner side of its antero-ventral surface. At this 
point an in-turning of ectodermal cells, in the form of a blind pit, 
develops, and later this pit, deepening to become a tube, forms the 
mouth cavity. Its inner end is from the beginning in contact with 
the. anterior end of the digestive tract, or else it connects with the 
latter soon after its formation. The two flatten against each other, 
the cells draw away in the middle of the region of contact, and the 
cavity of the new mouth becomes continuous with the cavity of the 
old digestive tract. The mouth lies at first nearly terminal in posi- 
tion (Fig. 57, E\ but by the forward growth of the body wall over 

1 In some species the two proliferating regions seem to be in contact above from the 
beginning (Hepke, in Nats), 



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THE ORIGIN OF NEW CELLS AND TISSUES 1 93 

and in front of the mouth to form the prostomium, the mouth comes 
later to lie more on the ventral surface. The short tube produced by 
the in-turned ectoderm forms only a short part of the digestive tract. 
It leads from the mouth opening to the new pharynx, and forms, 
therefore, only the buccal cavity. A similar ectodermal tube, the 
stomodaeum, which develops in the egg-embryo, becomes not only 
the buccal chamber, but also the lining of the pharynx. The latter 
is, therefore, considered an ectodermal structure in the embryo. On 
the other hand, in the regenerated head the lining of the new 
pharynx arises from the anterior part of the endodermal digestive 
tract We find, therefore, that the same organ, the pharynx, may 
arise in the same animal from distinct "germ- layers." This result 
also has an important bearing on our ideas concerning the value and 
meaning of the so-called "germ-layers," and has helped to bring 
about a revolution of current opinion as to the importance of these 
layers. 

The preceding account of the development of the head has shown 
that while certain of the new organs and layers arise from the same 
organs of the old part, yet this is not true for all of them. Thus 
while the ectoderm gives rise to ectoderm, the new muscles do not 
appear to come from the old ones, or even from other mesodermal 
tissues, but from the ectoderm. The old digestive tract gives rise to 
the greater part of the new one, but the new pharynx comes from 
the old endoderm, and not from the in-turned ectoderm. The nervous 
system does not arise from the old ventral cord, but from a prolifera- 
tion of ectoderm. It has, thus, the same origin as the nervous sys- 
tem of the embryo. The origin of the new blood vessels has not 
been satisfactorily made out. The seta sacs arise from ectodermal 
pits as in the embryo. 

In regard to the origin of the new mesoderm, the evidence is still 
insufficient, I think, to show that cells derived from the old muscles 
or peritoneum take no part in the formation of the new muscles and 
peritoneum; but that the greater part of the new muscles, etc., comes 
from the proliferated cells. can scarcely be doubted. This latter dis- 
covery loses none of its significance, however, even if it should prove 
true that the old muscles, etc., contribute something to the new part. 
It is also not entirely disproven that the ventral nerve-cord does not 
take a small share in the development of the new cord. 

The regeneration of a new tail-end in these same forms appears 
to take place in much the same way as the head. The cut-end 
quickly closes ; later a layer of ectoderm appears over the posterior 
surface, and the new part bulges out and becomes dome-shaped. 
A paired, or in some species a single, region of proliferation develops 
from the ectoderm, that gives rise to the new ventral nerve-cord. 

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194 



REGENERATION 



Lateral proliferations of ectoderm produce, according to some 
writers, the material out of which the mesoderm of the new tail is 
formed. Randolph, on the other hand, has described the new meso- 
derm as arising from the old, especially from certain large peritoneal 
cells that are found throughout the body. The cut-end of the diges- 
tive tract closes, and later new cells develop at its posterior end. An 
in-turning of ectoderm, in the form of a pit, fuses with the posterior end 
of the digestive tract and establishes communication with the outside. 





B 




Fig. 58. — After Hescheler. Regeneration of anterior end of earthworm. A. After four days, 
/y. Afte^r eleven days. C After twenty-five days. D. After twenty-one days (younger in- 
dividual). 

The regeneration of the anterior end of the earthworm has been 
carefully worked out by Hescheler, and although on account of the 
greater complexity of the process the results are not so decisive as 
those just described, yet in many respects they are in agreement. 
In Hescheler's experiments only four or five anterior segments were 
cut off. The closing of the cut-end is somewhat different from that 
in lumbriculus. A plug of cells soon forms over the end (Fig. 

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THE ORIGIN OF NEW CEJJ.S AND TISSUES 1 95 

58, A). The new cells appear to be lymph cells. Although this 
mass of cells may be quite large, the cells do not seem to form 
later any of the organs in the new head. The presence of these cells 
makes it very difficult to work out the origin of the other cells that 
appear later. Owing to the absence of this lymph plug in lum- 
briculus and nais it is easier to follow in them the regenera- 
tive processes. In the midst of these lymph cells spindle-like cells 
soon appear whose origin is obscure, but Hescheler thinks it im- 
probable that they are transformed lymph cells, although they are 
completely intermixed with the latter. The spindle-cells arrange 
themselves later in regular bands, that appear to be extensions of the 
longitudinal muscles. A few days after the operation, the lymph 
plug is covered over, beginning at the edge, by the ectoderm. The 
new ectodermal cells arise from the old ectoderm, and seem to extend 
over the lymph plug by a sort of migration process. Division of the 
cells does not occur at this time. These covering cells are at first all 
alike, the characteristic gland cells of the ectoderm being absent. 
The digestive tract withdraws somewhat from the outer cut-surface, 
and its end closes. The closed end abuts against the inner surface 
of the lymph plug. The next changes are initiated by the appear- 
ance of karyokinetic divisions in all the tissues of the new part, which 
lead to a rapid growth and elongation. Dividing cells are found in 
the new, as well as at the border of the old, ectoderm, where the 
new and the old parts are continuous. At this stage there appears 
in the lymph plug another kind of cell, that seems to arise, in part 
at least, from the ectoderm by an in-wandering of new cells. Other 
new cells may come from the edge of the old muscles, but it is 
not clear whether they come from a transformation of muscle cells, 
or from undififerentiated cells lying in the old muscles. In addition to 
these sources of new cells, it appears not improbable that cells may 
separate from the end of the digestive tract. 

Nerve fibres push out from the end of the ventral nerve-cord into 
the new part, and groups of cells, often in process of division, appear 
in the old ganglia, even in those that lie a long distance from the anterior 
end. It is not improbable, Hescheler thinks, that new cells, as well 
as fibres, grow forward from the most anterior end of the nerve-cord 
into the new part. A mass of nerve cells and fibres appears in front 
of the old nerve-cord, and extends upwards and around the digestive 
tract, to meet over the anterior end. of the latter in another mass of 
cells that have arisen from an early in-wandering of ectodermal cells. 
It is not improbable that the masses around the digestive tract (the 
commissures) and also the new ventral cord may also include cells 
that have had the same origin. 

A tubular invagination of ectoderm is formed at this time at the 

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196 



REGENERATION 




anterior end. It meets the anterior end of the digestive tract ; the 
two fuse, and the communication of the digestive tract with the out- 
side is established. The pharynx develops from the anterior part 

of the digestive tract, which 
after Hescheler*s operatioa 
may contain some of the origi- 
nal ectodermal stomodaeum, 
since only five of the anterior 
segments were cut off, and 
the embryonic stomodaeum 
extends somewhat behind this 
region. In another experi- 
ment, carried out by Kroeber, 
somewhat more of the anterior 
end was removed, but the re- 
sult was the same (Fig. 59), so 
that it is clear that the new 
pharynx may be formed from 
the old endoderm. 

Hescheler leaves several 
points still unsettled, more 
especially the origin of the 

Fig. 59. — After Kroeber. Regeneration of anterior CcUs that glve risC tO the neW 

end of Allolobophora fcetida, after removal of six % , u i. •*. • i *, 

segments. The first stomodoeal invagination mUSCUlatUrC, DUt it IS almOSt 

had been destroyed The new pharynx is devel- impossible tO make OUt their 

opmg from the endoderm. ^ 

origin in this animal, owing to 
the presence of the lymph cells. Hescheler's discovery that the cells 
of the lymph plug do not themselves, in all probability, contribute to 
the new part, is an important result, and shows that these seemingly 
undifferentiated cells do not possess the power of giving rise to the 
different kinds of new tissues. The in-wandering of cells into this 
solid plug from the ectoderm, and perhaps also from other sources, 
and their subsequent union to produce the definitive organs, is also a 
point of capital importance, especially as it puts us on our guard 
against a too ready acceptation of the view that all cells in a mass 
that have the same general and undifferentiated appearance have had 
a similar origin, and in showing that apparently indifferent cells may 
really carry with them into the new part those characters that deter- 
mine their fate. Other cells, apparently equally undifferentiated, 
and lying in the same position, may have quite different possibilities. 
In the vertebrates, the regeneration of the tail and limbs of am- 
phibia and of the tail of lizards has been studied by a number of 
investigators. The regeneration of the tail of several urodeles 
and of the larva of the frog was investigated more fully by Fraisse 

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THE ORIGIN OF NEW CELLS AND TISSUES 1 97 

('95) and by Barfurth ('91). If we examine first the results of 
Fraisse's study of the tail of urodeles, which have bony vertebrae, we 
find the following changes take place. The cut-surface is covered by 
the skin bending over the exposed part, accompanied by a migration 
of cells from the edge of the ectoderm. Only the unspecialized 
cells leave the old ectoderm to wander out over the cut-surface; 
gland cells and sense cells are entirely absent from the new ectoderm. 
These kinds of cells develop later out of the undifferentiated cells 
over the new part. The development of new vertebrae does not fol- 
low the embryonic method of development. In the embryo the 
endodermal notochord is first laid down, and around this and the 
nerve-cord mesodermal cells accumulate to form the skeletal tissue. 
Later the notochord is largely obliterated, as the vertebrae develop, 
pieces of it being left along the vertebral column. In the regeneration 
of the tail of the adult animal, the remnants of the old notochord 
(even if exposed by the cut) do not take any part in the formation of 
new tissue. In fact, there is no notochord formed at all. From 
the injured vertebrae, or at least from their covering of skeletal tis- 
sue, cells are proliferated, out of which a cartilaginous tube develops, 
enclosing the new nerve-cord, which is growing out from the cut- 
end of the old cord. In this tube centres of deposition of calcareous 
material are formed, and the new vertebrae are produced in this way. 
The new nerve-cord develops from the cut-end of the old cord, and 
more especially out of the cells of the lining epithelium of the canalis 
centralis. The new muscles develop from cells that arise from the 
old muscles. 

In the tadpole of the frog the regeneration of the tail takes 
place essentially in the way just described for the adult urodele, 
except that, there being only a notochord in the tail, only a notochord 
is regenerated. According to Fraisse, the new notochord develops 
from cells that arise from the sheath of the old notochord, and not 
from the vacuolated cells of the notochord itself. The notochgrd 
cells are, he states, derived from the endoderm of the embryo,^ while 
the sheath arises from the mesoderm ; hence the newly regenerated 
notochord that arises from the sheath of the old one comes from a 
different germ-layer. Exception may be taken to this statement, 
because in the frog's embryo the notochord develops from tissue that 
is at first perfectly continuous with the mesoderm, and, in fact, may 
be called mesoderm ; also because it is probable, in the light of more 
recent research, that both the notochord and its sheath have exactly 
the same origin. 

^ This seems to be true for urodeles, but whether it is true for the anurans is rather a 
question of definition, as I have pointed out in my book on The Development of the frog's 

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1 98 REGENERA TION 

It is known that the tail of lizards breaks ofif generally at a definite 
region near the base, and that the break does not occur between the 
vertebrae, but in the middle of a vertebra — in some species the seventh 
caudal. The vertebrae are thicker at their ends than in the middle, 
and are firmly held together by intervertebral cartilages. The cen- 
tres of the caudal vertebrae are the weakest links in the chain, or at 
least the place at which the vertebral column is most easily broken in 
response to the contraction of the tail-muscles.^ Fraisse and others 
speak of this arrangement as an adaptation for breaking off the tail. 

The new tail that regenerates does not contain a new series of 
vertebrae, as does the new tail of the salamander, but, instead, a car- 
tilaginous tube that is attached to the half of the broken seventh 
caudal vertebra. 

The regeneration of the new tissues of the tail of the lizard takes 
place as follows : A scab forms over the cut-surface, composed in part 
of clotted blood, in part of broken-down tissues from the injured cells. 
In the course of a week the necrotic tissue falls off, and a smooth sur- 
face of ectoderm is found covering the end of the tail. The new ecto- 
derm appears to come from the old, but its method of development 
has not been studied. The deeper layer of the skin of the lizard is 
composed of mesodermal connective tissue, and in the new part this 
layer arises from the connective tissue of the old part. The tissue 
that forms the cartilaginous tube of the new tail develops from the 
skeletal tissue of the broken vertebra. The remnants of the old noto- 
chord, that are present in the vertebra, have nothing to do with the 
new structure, nor does the new tube represent in any way a noto- 
chord, but it appears to be a structure sui generis. In later stages, 
osseous plates may be formed in the cartilage, but these are too 
irregular to be compared to vertebrae. A tube grows out from the 
cut-end of the nerve-cord, which in some forms, as Fraisse shows, 
is only an extension of the lining epithelium of the nerve-cord. In 
other forms it is possible that other cells of the old cord may also grow 
backward, divide, and produce new cells. The fine thread that is 
formed in this way does not send out any nerve fibres into the sur- 
rounding parts. In Angnis fragilis, however, a few ganglion cells are 
present in the new cord. It is probable, Fraisse states, that while the 
new tube is morphologically a nerve-cord, yet physiologically it is not 
functional in any of the reptiles. 

The new muscles come from the old ones. Fraisse thinks that the 
new muscle fibres come from the so-called " spindle fibres " that split 
off from the primitive muscle bundles. These fibres, Fraisse believes, 
originate normally during the process of physiological regeneration of 

1 The attachments of the muscles may be the cause of the break in the middle of the 
vertebrae, rather than between two vertebrae. 



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THE ORIGIN OF NEW CELLS AND TISSUES 199 

the muscles, and also after injury to the muscles. From these spindle 
cells the new muscle fibres develop in the same way as the muscle 
cells of the embryo. 

Fraisse sums up the results of his studies of regeneration as fol- 
lows: (i) Both in amphibians and reptiles, injured tissues can only 
produce new tissues like themselves. The leucocytes assume only 
the function of nutrition and of devouring the broken-down parts of 
tissues. They never become fixed tissues — neither connective tissue 
nor any other sort. (2) All tissues are capable of regenerating them- 
selves, either directly out of their differentiated elements, or out of a 
matrix. As a matrix for the epidermis, there is the Malpighian layer 
of the skin; for the central nervous system, the epithelium of the 
central canal of the nerve-cord ; and for the musculature, the spindle 
fibres. 

Fraisse also formulates the following general statements : {a) Re- 
generation is neither a pure recapitulation of the ontogeny nor of 
the phylogeny. The process is rather a hereditary one, with which 
complicated adaptations of the tissues are often involved that fol- 
low the laws of correlated development, {b) We cannot explain the 
phenomenon of regeneration, as the result of wounding the tissues, 
or as the outcome of an increase in the food supply, or as due to the 
removal of a resistance to growth. Far more important are the prin- 
ciples covered by the former paragraph, {a). 

Barfurth has studied in detail the regeneration of the tail in some 
amphibia ; and his results, while not covering as much ground as do 
those of Fraisse, yet give a more detailed account of the origin of the 
new tissues. Barfurth*s results on triton and siredon are not essen- 
tially different from those of Fraisse. In the tadpole of the frog, Bar- 
furth finds that the notochord regenerates from the sheath of the old 
notochord. In the larval urodele, he finds that the new notochord 
arises as in the tadpole, and not from the skeletal sheath, as Fraisse 
maintains. In very young larvae of siredon the chordal cells them- 
selves seem to give rise to the cells of the new notochord. In older 
larvae, in which the skeletal tissue is developed around the notochord, 
regeneration takes place both from this tissue and also from the sheath 
of the notochord. He concludes that in the regeneration of the new 
notochord, and also of the skeleton, the origin of the cells depends 
upon the developmental stage of the supporting tissues. 

In regard to the regeneration of the muscles, Barfurth comes to 
the following conclusions: In very young larvae of siredon, the de- 
generative changes in the muscle cells are often very sUght. Regen- 
eration takes place by growth from and the displacement of the old 
muscles. During this time bud-like terminal and lateral formations 
occur in the muscle fibres. These outgrowths contain nuclei and 

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200 REGENERATION 

form sarcoblasts ; and these pass into the new part, where they make 
the new muscle fibres in the same way as do the cells of the embryo. 
In older larvae of the frog, and in mature animals in general, the 
changes are more complicated. Two processes can be distinguished: 
(a) degenerative and {b) regenerative, (a) Broken-down muscle 
fibres that have been cut, and torn-off pieces of muscle fibres, are 
found present. There follows an accumulation of leucocytes and of 
giant cells. The nuclei in the degenerating muscle fibres atrophy, 
and the substance of the fibres breaks down, {b) The muscle fibres 
split lengthwise to form spindle fibres, and there is an increase in the 
number of nuclei at the same time. Sarcoblast-like outgrowths of the 
old muscle fibres are formed, which produce the sarcoblasts that 
become new muscle fibres. 

Barfurth agrees with Fraisse in two main points, viz. that all the 
tissues of the tail have the power of regeneration, and that each tissue 
produces only tissue like itself. The law which KoUiker attempted to 
establish, viz. that the elements of the formed tissues have lost the 
power of producing other kinds of tissue, — the law of the specification 
of the tissue, — is supported by these results of Fraisse and of Bar- 
furth, but is contradicted, as has been shown above, by the results on 
the earthworm, and also as we shall see even in the amphibia, as for 
instance in the regeneration of the lens of the eye. 

Spallanzani^ was the first to study the regeneration of the 
limb in salamanders, and found that the skeleton in the new part is 
like that in the normal limb. Bonnet, Philipeaux,^ as well as other 
naturalists,^ also examined the regeneration of the limbs of salaman- 
ders. Gotte (*79) has studied the embryonic development and the 
regeneration of the limb of triton, especially in regard to the origin 
of the new bones. He found that the skeleton develops in much the 
same way in the embryonic limb and in the regenerated limb, and the 
process in the latter may be said to repeat that in the former. This 
is especially true for the regeneration of the limb of a very young 
larva, but the older the larva the more it departs from the embryonic 
type of development. If the limb is cut off through the upper arm, 
or through the thigh, new tissue develops over the cut-end. If the 
larva is quite young, so that formation of the cartilages in the leg has 
not gone very far, the new tissue differs very little from the old ; but 
if the leg of an older larva is amputated, the difference between the 
old and the new parts is more striking. If the bones of the leg have 

^ Prodromo, 1768. 

2 Philipeaux, Comptes rendm de VAcad, des sciences dt VTnstittit de France^ Annce 
1866, 1867. 

* Todd (^Quarterly Journal of Science, Literature^ and Arts, Vol. XVI), Blumenbach, 
Treviranus, Von Siebold. 



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THE ORIGIN OF NEW CELLS AND TISSUES 20I 

become ossified, the transition from the old to the new part is at first 
very sharp. The new tissue, that will make the new cartilages of the 
new limb, develops as a cap over the cut-end of the old bone. 
Gotte does not give an explicit statement in regard to the origin 
of the new cartilage, but his account leads one to suppose that it 
develops from the old cartilage or from some part of the bone. 
This is, in fact, the case, as I have observed in preparations of the 
regenerating leg of Plethodon cinereiis^ in which the new cartilaginous 
tissue comes from the periosteum of the old bone. Gotte shows 
that two long rods of tissue are formed, that are separate for the 
greater part of their length. They give rise to the two bones of the 
lower leg, or forearm, as the case may be. The broken end of 
the femur or humerus also completes itself by a short cartilaginous 
cap, which is at first continuous with the two rods just described. 
The ends of these two rods break up into a series of pieces that 
form the tarsalia, or the carpalia, and the digits. Two digits are first 
formed, and the others are added as outgrowths from the side of one 
of the two rods. It is important to note that the new cartilages are 
formed, in large part, out of a continuous substratum (or rather of 
two) which separates into proportionate parts to produce the elements 
of the new limb. 

The regeneration of the muscles of the limb of an adult animal, 
plethodon, has been recently worked out by Towle. The leg was 
cut off in the middle of the forearm. Extensive changes take place 
in all the muscles that extend across the level of the cut. The old 
fibres in the lower end of the muscle, />. those near the cut-end, 
disintegrate, and the number of nuclei greatly increases. The divi- 
sion of the nuclei seems to be direct, each retaining some of the 
old muscle substance about itself. From some of these cells the new 
muscle tissue is formed in the new part. Higher up in the forearm 
the muscle fibres break down to a smaller extent, and still higher up 
some of the old fibres may remain intact. New muscle fibres are also 
formed in the old muscle, especially in the region near the cut-end. 

The process of regeneration has not been so fully worked out in 
any other vertebrates as in those described in the preceding pages, 
although the regeneration of sutj^le tissues or organs in the verte- 
brates has been extensively investigated. In all such cases it is found 
that like tissues give rise to like. 

In the planarians it has been found that during regeneration the 
ectoderm covers the exposed surface, and from it arises the new ecto- 
derm ; the digestive tract appears to come in part from the old tract 
and in part from the middle-layer cells ; the nervous system appears 
also to develop out of the middle-layer cells that are found scattered 
through the body. These cells seem to form a sort of reserve supply 

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202 REGENERATION 

that gives rise to the digestive tract, nervous system, and middle-layer 
cells in the new parts. From them also arise the new pharynx, and the 
lining of the pharynx chambers, as well as some other structures. It 
is impossible to say at present whether one and the same kind of cell 
may give rise to all these structures, or whether different kinds of 
cells are present in the middle layer, that cannot be distinguished 
from each other by the methods at present at our command. 

The changes taking place in the tissues of those animals that 
regenerate by morphallaxis have been only quite recently carefully 
investigated. Bickford stated that in tubularia the old differentiated 
tissue changes over directly into the tissue of the new part, and 
Driesch confirmed this statement. Stevens has studied by means of 
serial sections the different changes that take place. Division of both 
ectodermal and endodermal cells is found to occur, but especially the 
ectodermal. Whether all the ectodermal cells divide, or only some of 
them, is difficult or impossible to state, but whether this happens or 
not, all the old region goes over into the new hydranth. 

The changes that take place in hydra have been recently worked 
out in my laboratory by Rowley, who finds that a certain amount of 
division takes place in the old cells, especially in the ectoderm. The 
division of the cells is not a very active process, and it seems not 
improbable that many of the old cells go over without dividing into 
the new part. 

One of Trembley's most celebrated experiments was that in which 
hydras were turned inside out (Fig. i, A, B)y so that the ectoderm 
came to line the inner cavity and the endoderm to cover the outer 
wall. The tentacles were not everted but remained sticking out of 
the mouth of the everted animal. Their openings, or arm-holes, 
therefore, appear on the outer surface of the body. In order to 
prevent the everted hydra from turning itself back again, as it tends 
to do, Trembley pushed a small bristle crosswise through the wall of 
the body. Finding the hydras still sticking on the bristles the next day, 
he concluded that they had not returned to their former condition, but 
that the outer layer (the endoderm) had changed its character so that 
it became ectoderm, and the inner layer (the ectoderm) became 
endoderm.^ The experiment seemed to show that the two layers 
could change their specific character and be transformed into each 
other according to their position in the animal. These remarkable 
results were not challenged until 1887, when Nussbaum repeated the 
experiment and showed that Trembley had overlooked an important 
fact. It was found that even the bristle pushed through the body 
does not prevent the hydra from regaining its original condition, 
although it may delay the turning back. If the turning back can be 

^ How the tentacles could have gotten into their normal position is not explained. 



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THE ORIGIN OF NEW CELLS AND TISSUES 203 

prevented, the animal dies. Nussbaum showed how the turning back 
takes place in an animal while it remains on the bristle. The everted 
foot-end begins first to turn back, pushing into the central cavity. 
When it comes to the bristle it passes to one side of it, and continuing 
to turn back the foot passes out of the mouth, drawing the rest of the 
body after it.^ • The last act of the turning can take place only by 
tearing away through one or both sides, and this is often done. The 
bristle may still remain sticking to the body through one side, or even 
remain through both sides if the body has, after tearing through, 
healed up around the bristle. The process of turning back may take 
place quite quickly, and had been overlooked by Trembley, who 
trusted too confidently to the presence of the bristle sticking through 
the animal. 

The method by which the turning back of the layers takes place 
was not, it appears, clearly described by Nussbaum in his first paper, 
for his account seems to imply, in certain passages, that the ectoderm 
may slide over the endoderm during the process, rather than that 
both layers always turn together. Ischikawa, who studied the problem 
later, gave a clearer account of the method of turning back. Nuss- 
baum has stated in a later paper that he had described essentially 
the same process. 

In conclusion, it can be definitely stated that a transformation of 
ectoderm into endoderm cannot take place in hydra. Ischikawa also 
tried removing the endoderm from a piece by spreading it out and 
then killing the inner layer by weak acid applied with a brush, but 
pieces of this sort failed to regenerate a new endoderm. 

Tower has recently stated that if a living hydra is put into a 
strong light from an arc lamp of 52 volt 12 ampere capacity, that 
i^ focussed on the animal (after passing through an alum cell), the 
ectoderm cells fly off, but if the animal is kept, it subsequently pro- 
duces a new ectoderm. Whether all the ectoderm is lost, or only the 
larger neuro-muscular cells, was not made out. 

One of the most unexpected discoveries of recent times in con- 
nection with the problem of regeneration is the renewal of the 
extirpated eye of triton and salamandra. Colucci first discovered 
in 1 89 1 that if the eye is partially removed a new eye develops from 
the piece that remains and that the new lens develops from the margin 
of th^ bulb. Wolff, a few years later, not knowing of Colucci's 
results, also found that after extirpation of the lens of triton, by 
making an incision in the cornea, a new lens develops from the edge 
of the old iris. Wolff pointed out the great theoretical importance 
of this result. The experiment has been repeated and confirmed by 

1 The foot sometimes pushes out through one of the slits made by the bristle instead of 
out of the mouth. 



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204 



REGENERATION 



a number of more recent workers, so that there remains no question 
as to its accuracy. 

After the removal of the old lens the wound in the cornea 
quickly heals, and in the course of two or three weeks a thickening 
appears at one point at the edge of the iris (Fig. 60, A), The cells 
that produce this thickening are the ordinary deeply pigmented cells 
of the iris, where the outer layer of cells of the iris becomes continu- 




FlG. 60. 
lens. 



— After Wolff. Regeneration of lens of eve of Triton. 
B, C, D. Later stages of same. E. After t'ischel. Whole eye with regenerating lens. 



A. Edge of iins with beginning 
Jen 



ous with the inner layer. The cells increase in number and produce 
a spheroidal ball that hangs down into the space formerly occupied 
by the lens (Fig. 60, E). The cells become clearer by absorbing 
their pigment and arrange themselves concentrically as in the normal 
lens. When fully formed the new lens separates from the iris and 
occupies the normal position. 

The most surprising fact in connection with the development of 

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THE ORIGIN OF NEW CELLS AND TISSUES 20$ 

the new lens is that it arises from a part of the body from which the 
lens of the eye never develops in the embryo of this form or of any 
other vertebrate. In the embryo the lens develops from the ecto- 
derm at the side of the head and only secondarily unites with the 
optic cup, that has come from an evagination of the anterior wall of 
the fore brain. In the regeneration of the adult lens, however, the 
ectoderm covering the eye takes no part in the formation of the new 
lens, — in fact, it is separated from the eye by the thick inner, meso- 
dermal layer of the cornea. The lens develops, as has been stated, 
from the already differentiated layers of the iris. It is a point of 
further interest to notice that the cells that form the transparent lens 
come from the iris cells that are in part at least filled with black pig- 
ment. If this pigment remained in the cells the new lens, while it 
might be structurally perfect, would be physiologically useless. The 
pigment disappears, however, as the lens develops. In this case we 
find a highly specialized organ, the lens, developing out of tissue 
also specialized in another direction. It does not simplify the prob- 
lem to point out that the lens and the iris are both parts of the eye, 
since they have arisen from different parts of the body and have 
only secondarily come into apposition with each other. Colucci was 
contented to point out that both the embryonic lens and the regen- 
erated one come from ectoderm and that the result can be brought 
into harmony with the " germ layer " hypothesis. 

Wolff has called attention to the fact that the new lens arises 
from the upper edge of the iris, and that this is obviously the most 
advantageous position in which it could develop from the iris, since 
by its own weight it falls into place as it develops. If the lens had 
developed from any other point of the margin, its position would be 
less advantageous, as it might not be brought into its proper position. 

Fischel, who has more recently studied the regeneration of the 
lens in the larvae of Salamandra mactdata, finds that after the 
removal of the lens the iris is thrown into wrinkles or folds and may 
stick at first to the cut-edge of the cornea. After the cornea has 
healed, the iris returns to its normal position. He finds that the 
first changes are more or less alike around the entire rim of the iris 
and involve a partial absorption of the pigment, a separation of the 
inner and outer layers at the edge, and a swelling of the margin. 
These changes go only a little way in those parts that do not pro- 
duce a lens, but at the upper edge of the iris they go farther and 
lead to the formation of a lens in that region. He finds also that a 
new lens develops in animals kept in the dark as well as in those 
kept in the light, and in the same way. 

Fischel also tried the effect of removing a part of the upper edge 
of the iris at the time when the lens was extirpated, in order to see 

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206 REGENERATION 

if, in the absence of this part, the lens would develop from other 
parts of the uninjured margin of the iris. He found that the new 
lens still comes from the upper edge of the iris from the part left 
after the operation and not from the intact edge in other parts. 
This seemed to show that an injury to the iris is in itself a stimulus 
that starts the formation of a lens. This conclusion is made prob- 
able by the results of other experiments in which the iris was stuck at 
several points, when new lenses began to develop at several of these 
regions of injury. In some cases Fischel found that two or more 
lenses began to develop when the iris had not been intentionally 
injured ; but it is not improbable that some sort of injury may have 
been effected when the lens was removed. Fischel, as has been said, 
removed extensive portions of the upper part of the iris and found 
that a new lens could be formed at the cut-edge, even in the region 
of the pars ciliaris ; and, even after the removal of the entire upper 
part of the iris, lens-like structures may appear in the inner or retinal 
layer of the remaining region. 

If instead of removing the lens it is displaced by pressing on the 
cornea until the lens leaves its normal position and comes to lie in 
the vitreous humor, a new lens develops from the edge of the iris, as 
though the old lens had been entirely removed from the eye, but in 
the experiments in which this was done the new lens was not well 
developed. The result shows that it is not necessary that the old 
lens be removed from the eye in order to induce the regeneration of 
a new one, but only that the lens lose its normal position in the eye. 

In regard to the stimulus that determines the development of the 
lens, Fischel agrees with Wolff that gravity has a share in producing 
the result. The absence of the old lens from its normal position, 
as well as the wrinkling of the cornea, may also enter in as factors. 
Fischel takes issue with Wolff as to the interpretation of the result 
as an adaptation, and states that "the organism always responds to a 
change of relation in only one way, whose direction is already deter- 
mined by internal structural relations, without regard to whether 
the result is adaptive or not. The response follows each stimulus in 
a way determined by the limited possibilities of the cells. With 
such a uniformity in the reaction, the idea of a fundamental adapt- 
ability cannot be connected, since the reaction that appears to us to 
be adaptive in a series of complicated changes may be non-adaptive 
in another series." 

Whether Fischel has here really met Wolff's argument is, I think, 
open to question. It does not alter the result to show that factors 
already existing enter into the process, so long as the organism is so 
constructed that just those factors are present that bring about a use- 
ful response. That the response may be sometimes imperfect does 

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THE GERM-LAYERS IN REGENERATION 20/ 

not affect seriously the argument — in fact, it makes the case all the 
more remarkable if these imperfect attempts are in the direction of 
useful responses. Fischel sums up his conclusions as follows : " It is 
not necessary, and it is irreconcilable with the facts, to describe the 
formation of the lens in a teleological sense, and to bring this case 
forward as a proof of the universal application of a teleological 
principle. As has been already stated, the facts in regard to this 
case show much more clearly that the organism reacts to each 
change always in a manner that corresponds to its limited possibili- 
ties without regard to a teleological principle. A planarian, for in- 
stance, responds to a stimulus and makes a new head, even when 
it possesses one or more already ; a tubularian produces a hydranth 
at its basal end, if this end is freely surrounded by water ; an actin- 
ian forms a new mouth on the side of its body, etc. ; so also do the 
cells of the pars ciliaris, and the pars iridica retitKE differentiate into 
lens fibres. Working blindly, without respect to the consequences 
as far as they concern the whole, the one thing only is pro- 
duced for which the conditions are present that bring about its 
formation in the cells." 



THE PART PLAYED BY THE " GERM-LAYERS'' IN REGENERATION 

Our examination of the origin of the tissues and organs in the 
new parts has shown that in most cases the old tissues give rise to 
the same kind of tissue in the new part; or in some other cases, 
as in the nervous system, the regenerating organs arise from the 
same "layer" as that from which they develop in the embryo. 
These facts have led many writers to state that the tissues and 
organs in the regenerated part arise from the same germ-layers as 
do the same parts in the embryo. It is supposed that ectoderm 
gives rise to ectoderm, and to those structures that arise from the 
ectoderm in the embryo, as, for instance, the nervous system, stomo- 
daeum, etc. The endoderm is supposed to give rise to endoderm, and 
to endodermal structures, and the mesoderm to mesoderm and its 
derivates. So fixed has this opinion become that it is not uncom- 
mon to find investigators proclaiming the triumphant success of their 
results, because they have been able to trace the organs in the regen- 
erated part to the same germ-layers that give rise to these organs in 
the embryo. Before deciding as to the value of this point of view, 
let us examine briefly the foundations of the so-called germ-layer 
hypothesis. 

The origin of this hypothesis goes back at least to 1759, when 
C. F. Wolff maintained his thesis that the digestive tract of the chick 
exists as a flat, leaf-like structure that subsequently rolls up into 

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208 REGENERATION 

a tube. He thought it probable that other embryonic organs might 
arise in the same way. His views made at the time no impres- 
sion on his contemporaries, and lay buried until 1812, when Meckel 
republished Wolff's work in a German translation. Pander, in 18 17, 
distinguished two layers in the early embryo, a serous and a mucous, 
and stated that later a third, vascular layer appears between the 
other two. Von Baer published in 1829 his celebrated memoir on 
the development of the chick, in which he made out two primary 
layers in the germ, the animal and the vegetative layer, and held that 
each of these separates into two to produce the four embryonic 
layers. Remak, in 1851-1855, gave a more precise description of the 
germ-layers, and stated that from the innermost layer, the epithelium 
and glandular cells of the digestive tract arise (including the lining 
of the glands that open into the digestive tract). From the outer- 
most layer he showed that the integument and sense organs and the 
nervous system develop, and from the two middle layers develop the 
muscles, blood, excretory, and reproductive organs. By the term 
" germ-layers " was meant at this time only that the embryo is formed 
out of sheets. 

Huxley in 1849 pointed out that a medusa is made up of two 
layers, an outer and an inner, and called attention to their possible 
equivalency to von Baer*s serous and mucous layers. This idea of a 
resemblance between the layers of an embryo and of an adult of 
a lower form furnished the starting-point for the more modern for- 
mulation of the germ-layer hypothesis. Kowalevsky's work on the 
development of a number of the lower animals showed that there is 
present in many forms a two-layered stage, or gastrula, formed by 
an in-turning of the wall of the hollow blastula. In this way two 
germ-layers are established, an outer and an inner, that correspond 
to the ectoderm and to the lining of the digestive tract, or endoderm. 
While Kowalevsky's work did much toward laying the foundation of 
the modern study of embryology, he himself indulged in very little 
of the sort of speculation that came into vogue a few years later. 
Kowalevsky's discovery of the gastrula stage in the embryos of many 
different groups has been fully confirmed and extended, but the elabo- 
rate speculations that have been built up on this as a basis have 
gone far beyond the evidence, and, for a time, drew the attention of 
embryologists away from more important problems. Haeckel took a 
more extreme position than most of his contemporaries, and assumed 
that the gastrula stage that occurs in so many of the groups of meta- 
zoa corresponds to an ancestral, two-layered adult animal, the gas- 
traea, from which all the higher forms have descended. The presence 
of the gastrula in the development was interpreted as a " repetition " 
of this ancestral adult stage. Thus the two primary layers are sup- 

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THE GERM-LAYERS IN REGENERATION 209 

posed to have an historical meaning.^ Embryologists soon began a 
search for a similar mode of interpreting the middle germ-layer, or 
layers, which led, amongst other views, to the formulation of the 
"gut-pouch hypothesis." From this point of view the body cavi- 
ties, or coelomes, are supposed to have been originally sac-like out- 
growths from the digestive tract of an ancestral adult animal. Later, 
these coelome sacs are supposed to have been shut off from connec- 
tion with the digestive tract — their cavities becoming the body cavi- 
ties, and their walls giving rise to the mesodermal organs. The 
formation of pouches from the walls of the archenteron of the embryo 
in several groups of animals has been interpreted as a repetition of 
the ancestral adult animal. 

A comparison of the germ-layers in different forms very soon 
led to an attempt to " homologize " the layers in different animals. 
If the layers have had historically the same origin, or appear in the 
same way in the embryos, or give rise to the same organs, they are 
said to be homologous. In the absence of a knowledge of the first 
two of these conditions it is generally considered sufficient, if it can 
be shown that similar organs arise from a layer, to " homologize *' 
that layer in the two forms. The study of embryology soon became 
a search for homologies. The results led to inextricable difficulties 
and innumerable contradictions until, a reaction setting in, many 
embryologists became sceptical in regard to the value of this entire 
method of study. 

The results of a detailed study of the process of cleavage in a 
number of groups have helped, perhaps, to clear the way for a sounder 
conception. It has been found that the cleavage of the ^gg in mem- 
bers of the groups of annelids, mollusks, and turbellarians is ex- 
tremely similar — so similar, in fact, that it seems hardly possible that 
they could be due to chance, especially as the series of cleavages is 
quite complicated. The discovery of these similarities led at once 
to comparison, and comparison to the establishment once more of 
homologies, and the homologies led again to contradictions, until at 
present scarcely any two workers agree as to a criterion of homol- 
ogy .^ Leaving this question aside, however, and fixing our attention 
only on the similarity of the process of cleavage, we are justified, I 
think, in looking for an explanation of the similarity in some sort of 
an historical connection. We can eliminate, I think, without discus- 
sion the possibility of this type of cleavage representing an ancestral 

* I have given elsewhere (^The International Monthly^ March, 1901) a fuller treatment 
of the gastraea theory from the historical point of view. 

* It may be pointed out that there may be really several kinds of homology, such as 
homology due to similar origin of the blastomeres, or to their position, or to their fate, etc. 
The confusion that has arisen may in part result from the attempt to make homologous 
parts agree in all points. 

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2 1 REGENERA TION 

adult animal. So far as the question of descent enters the problem, 
we can infer with some degree of probability that the groups in ques- 
tion may have come from a common group in which the ^g'g divided 
in much the sarhe way as we find it dividing at the present time. As 
a formal hypothesis this view meets with no serious difficulty, since a 
chain of forms, or a continuous living substance, connects the present 
animals with those living in the past ; and we may assume that the 
same factors peculiar to the egg of the ancestors are still present in 
the eggs of their descendants. This sort of explanation gives us no 
causal knowledge of the way in which the egg divides, nor does it 
preclude the possibility of new changes coming in that may entirely 
alter the form of the cleavage. Moreover, since we are dealing with 
a question of historical probability only, we cannot be certain that the 
same type of cleavage may not have arisen quite independently in 
each group. 

The argument in favor of the gastrula stage also representing an 
ancestral larval stage may be admitted as a remote possibility, but 
on evidence even far less satisfactory than that for the similarities of 
cleavage being accounted for by a common descent. That this gas- 
trula was ever an adult form we have no means of deciding, even as 
a matter of probability, and even if this could be made plausible it by 
no means follows that such an adult stage would become an embryonic 
stage of later forms. Consequently that part of the germ-layer theory 
that rests on such a supposed connection cannot be looked upon as 
much more than a fiction. 

But even granting that there is an historical, embryonic ^ connec- 
tion, its small importance for the scientific problems connected with 
embryonic development, and budding and regeneration has been 
shown by a number of recent discoveries, and nowhere more clearly 
than in the cases of the formation of new individuals by budding. 
As an example may be cited the method of development of the 
ascidian from the egg, and by means of buds. The work of Kowa- 
levsky, Delia Valle, Seeliger, and Van Beneden on the budding pro- 
cess of ascidians showed that there are some discrepancies between 
the bud development and the embryonic development. The more 
recent papers of Hjort, Oka, Pizon, Salensky, Lefevre, and others 
have shown very clearly that the germ-layer theory is inapplicable to 
the bud development in this group. The bud arises as a double- 
walled tube, or rather a tube within a tube, with a space between. 
The outer tube comes in all cases from the ectoderm of the animal ; 
the inner tube has a different origin in different species. In perophora, 
didemnum, and clavellina, the inner tube comes from endoderm ; in 
botryllus it arises from the ectoderm of the larval peribranchial or 

^ That is, one not depending on inheritance through adult forms. 

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THE GERM-LAYERS IN REGENERATION 211 

atrial cavity. In all these forms the inner tube gives rise to the new 
pharyngeal cavity of the bud, while this same cavity comes from the 
endoderm of the archenteron of the embryo. In the bud embryo the 
peribranchial space is also derived from the inner tube ; hence it is 
endodermal in the first series, and ectodermal in botryllus. In the 
egg embryo it is ectodermal In regard to the development of 
the nervous system there is some difference of opinion. A number 
of investigators have found that the new brain arises from the outer 
part of the inner or branchial tube, which has in most cases an 
endodermal origin. Seeliger and Lefevre believe the nervous sys- 
tem to arise from mesodermal cells that lie between the two tubes. 
It appears, nevertheless, that in several forms the brain really comes 
from the inner tube, which also gives rise to the branchial sac. There- 
fore, in those cases in which the inner tube is endodermal the brain 
has the same origin, and in the case in which the inner tube is ecto- 
dermal, the brain is ectodermal, but the pharyngeal sac has also an 
ectodermal origin. There is obviously no definite relation between 
the origin of these structures in the bud and in the egg embryo. 

A similar difficulty is met with in the Bryozoa in regard to the 
development of the egg embryo and the bud embryo. 

Braem, who has made a critical examination of the germ-layer 
theory,^ has found it impossible to give a morphological definition of 
a germ-layer, and has adopted a physiological criterion. He thinks 
that in whatever way a germ-layer arises, whether by folding, or by 
delamination, etc., it exists independently of its method or place of 
origin. A layer is not endodermal because it forms the inner wall 
of a gastrula, but it is endodermal because it develops into the diges- 
tive tract. The germ-layers of different forms are only similarly 
placed, but whether they are homologous will depend on other 
things. On this view the inner tube of the ascidian bud that gives 
rise to both digestive tract and to the nervous system is simply an 
indifferent layer until it gives rise to these structures. Its cells 
may be looked upon as indifferent, as are those of the blastula. 
Thus the diflSculty of the morphologist is not solved, but the knot is 
cut. For Braem the germ-layers are convenient terms, since he 
rejects any historical significance that they may have, and it is just 
this side of the question that the morphologist has attempted to work 
out. While the evidence shows that the germ-layers cannot have 
any such final attributes as embryologists have attempted to assign 
to them, and that Braem has called attention to the real and impor- 
tant problems connected with the study of development, yet it may 
still be admitted without endangering the newer point of view, that 
there may be also an historical question in connection with the germ- 

1 Bioiogisches Centralblatty XV, '95. 

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212 REGENERATION 

layers, if not in the sense of a repetition of an ancestral adult gastraea, 
yet in the sense that similarity in embryonic development may in 
some cases find its historical explanation in a common descent. 

If in the light of this discussion we turn to the phenomena of 
regeneration, we again find evidence showing that the germ-layer 
theory fails to apply in all cases. It has been pointed out that in 
lumbriculus, and in the naids, the new mesoderm is derived from the 
ectoderm, and does not come from the old mesodermal tissues. The 
mesoderm of the embryo in annelids is derived from one, and later 
from two, superficial cells of the blastula,^ that push in about the time 
of gastrulation. They cannot, at this time, be referred to one layer 
rather than to the other. It cannot be affirmed, therefore, that in 
regeneration, the mesoderm arises from a different layer from that in 
the embryo, but neither can this be denied. The most important 
point in this connection is that the new mesoderm comes from the 
ectoderm that is already differentiated, and not from the mesodermal 
tissues. It is clear, however, that while the lining of the pharynx in 
the embryo is ectoJermal, it is endodermal in the regenerated part. 

It is true that these cases are very exceptional, and that generally 
the new organs come from similar organs in the old part, but one 
established exception is sufficient to show that the traditional concep- 
tion of the germ-layers may be of little value, and since the hypothe- 
sis itself, out of which the idea in regard to regeneration from definite 
germ-layers has been formed, has been proven to be insuflHcient in 
other directions, the time is ripe to look for a more secure footing. 
It need hardly be added that the idea of a supposed necessity for an 
organ to arise from a definite germ-layer is so empty of all signifi- 
cance that we may well rejoice to be able to set it aside as a narve 
view that has had its day. Furthermore, a new series of problems 
has arisen in connection with the experimental work to be described 
in a later chapter. If, as seems probable, the question of the germ- 
layers will be merged into the much broader question of the origin 
of the specification of the tissues, we can in the future more profitably 
direct our attention to the experimental evidence that bears on the 
latter question. 

THE SUPPOSED REPETITION OF PHYLOGENETIC AND ONTOGENETIC 
PROCESSES IN REGENERATION 

It has been claimed that at times ontogenetic, and even phylo- 
genetic, processes are repeated during regeneration. Fraisse, for 
instance, who advocates this point of view, thinks that it has been 

^ A small amount of embryonic mesenchyme may come from some of the ectodermal 
quartettes of the embryo and produce the branching muscles of the head, but not the char- 
acteristic muscles of the trunk. 



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PHYLOGENETIC AND ONTOGENETIC PROCESSES 21 3 

too much neglected, and calls attention to several instances of what 
he believes to be cases in point. He thinks that Biilow is correct in 
his comparison between the method of development of the new tissue 
at the end of the tail in certain naids, and the method of gastrula- 
tion and formation of the mesoderm in the embryo. Later results 
have shown, however, that in several points Biilow^s observations are 
incorrect. The in-turning of ectoderm that Biilow compares with the 
process of gastrulation is connected with the formation of the ecto- 
dermal proctodaeum, and is not comparable with the development of 
the endoderm in the embryo. 

Gotte also, as we have seen, cites a case of resemblance between 
the regeneration of the limbs of the salamander and their mode of 
embryonic development. He finds the resemblances less marked as 
the animal becomes older. The resemblance is, however, not very 
close and of a rather general sort, and since the same structures 
develop in both cases out of the same kind of substance, it is not sur- 
prising that there should be some resemblances in the processes. This 
evidence is counterbalanced by the mode of regeneration of the tail 
in the adult of certain forms, and in the regeneration of the lens of 
the eye from the iris. 

Carriere finds that the eye of snails regenerates from the ectoderm 
in much the same way as the young eye develops. Granted that the 
eye is to come from the ectoderm in both cases, and that the same 
structure develops, it is not to be wondered at that the two processes 
have much in common. 

The mistake, I think, is not in stating that the two processes are 
sometimes similar, or even identical, but in stating the matter as 
though the regenerative process repeats the embryonic method of 
development. If the same conditions prevail, then the same factors 
that bring about the embryonic development may be active in bring- 
ing about the regenerative processes. In fact, we should expect 
them to coincide oftener than appears to be the case, but this may 
be due to the conditions being different in the young and in the 
adult. 

It has been claimed also that in some cases there is regenerated a 
structure like that possessed by the ancestors of the animal. ^ The 
stock example of this process is Fritz Miiller's result on the regener- 
ation of the claw of a shrimp, Atypoida protimirum} Fraisse and 
Weismann and others have brought forward this case as demonstra- 
tive. The animal is said to regenerate a claw different from any of 
those in the typical form, and one that resembles the claw of another 
related genus, Carodina, The value of evidence of this sort is not 
above question. Przibram has shown in other Crustacea that when 

1 Cosmos, Vol. VII, p. 388. ^ , 

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214 REGENERATION 

a maxilliped is cut off a structure different in kind often regenerates, 
but that after several months the typical structure returns. Do we find 
here an ancestral organ that first appears, and then gives way to its 
more modern representative ? If it resembled the maxilliped of any 
other crustacean, the evidence would, no doubt, be accepted by those 
who accept the evidence furnished by Miiller. What then shall we 
say to the case, first discovered by Herbst, in. which the eye of cer- 
tain prawns being cut off, an antenna-like organ regenerates ? Since 
these antennae are similar to those possessed by the same animal, 
shall we assume that it once had antennae in place of eyes ? 

Another comparison, that Fraisse has made, is worth quoting as 
showing how far credulity may be carried. In the regeneration of the 
tail of certain lizards pigment first appears in the ectoderm of the new 
part and then sinks deeper into the layers. Fraisse found a lizard on 
Capri in which the tail is pigmented throughout life, and although he 
did not know whether or not the pigment is in the skin he suggests 
that this lizard represents an ancestral condition, that is repeated by 
the regenerating tails of other forms. 

Boulenger ('88) pointed out that the scales over the regenerated 
tail of several lizards have a different arrangement from that of the 
normal tail, and furthermore, the new arrangement is sometimes like 
that found in other species. He claims that this shows that such forms 
are related, even where no evidence of their relation is forthcoming. 
That the conditions in the new tail may be different from those in 
the normal tail is shown by the absence of a vertebral column, etc. ; 
therefore that the scales also should have a new arrangement is not 
surprising, but the facts fail, I think, to show that there need be any 
genetic relation between the forms in question. That the conditions 
in the new tail might be like those in an ancestral form may be 
admitted, but this is very different from assuming that the results 
show a genetic relation actually to exist. The main point is that, 
even if the results should be nearly identical, it may be entirely mis- 
leading to infer that ancestral characters have reappeared. 

In some cases an extra digit or toe may regenerate on the leg of 
a salamander, and this too has been interpreted as a return to an 
ancestral condition. But Tornier has shown, as has been stated, 
that several additional digits, or even a whole extra hand, may 
be produced by wounding the leg in certain ways, and these too 
would have to be interpreted as ancestral, if the hypothesis is carried 
out logically. It has been shown by King that one or more additional 
arms may be produced in a starfish by splitting between the arms 
already present, and if we accepted evidence of this sort as having 
any value in interpreting lines of descent we should conclude ^ that 

^ King pointed out the fallacy of this argument. 

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PHYLOGENETIC AND ONTOGENETIC PROCESSES 21$ 

the ancestors of the starfish had six, seven, or more arms according 
to the number that can be produced artificially, etc. Therefore, until 
further evidence of a more convincing kind is forthcoming, we can 
safely, I think, decline to accept the results, so far knowa, as having 
any value in interpreting the relationships or the descent of the 
animals. 



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CHAPTER XI 
REGENERATION IN EGG AND EMBRYO 

Not only do adult organisms have the power of regeneration, but 
embryos and larval forms possess the same power, and even portions 
of the segmenting, and also the unsegmented, egg may be able not 
only to continue their development, but in many cases to produce 
whole organisms. Haeckel observed in 1 869-1 870 that pieces of the 
ciliated larvae of certain medusae, and even pieces of the segmented 
egg, could produce whole organisms. The more recent experiments 
of Pfluger (*83) and of Roux ('83) on the frog's egg mark, however, 
the beginning of a new epoch in embryological study. The expla- 
nation of this is to be found, I think, not only in the introduction of 
experimental methods, but also in the fact that Pfluger and Roux 
realized the important theoretical questions involved in their results. 

Pfliiger's experiments were made by changing the conditions 
under which the egg develops in order to determine what factors con- 
trol the development. Since these experiments were made with whole 
eggs, the problems of regeneration were not directly involved in his 
results, although his conclusions are of great importance in connec- 
tion with questions concerning the regeneration of the egg. A part 
of Roux's work dealt directly with the development of a new organ- 
ism from a piece of the egg or of the embryo. Roux*s principal dis- 
covery ^ (*88) was that a half -embryo develops from either of the first 
two blastomeres of the frog's egg, if the other blastomere has been 
injured or destroyed, but that subsequently the missing half of the 
embryo is " post-generated." Roux was led to this experiment by his 
discovery that the plane of the first cleavage of the egg corresponds 
very often to the median plane of the body of the embryo.^ This 
relation suggested that there might be some causal connection between 
the two phenomena in the sense that the first cleavage plane divides 
the material for the right side of the body from that of the left side. 
In a descriptive sense this would be, of course, true if the two planes 
do really correspond, and if there was no later shifting of material 

* Roux's earlier experiments in 1885, in which the unsegmented or segmented egg was 
stuck and a part of its contents removed, the remaining part making a whole embryo, will 
be considered in another connection. 

* This had been first discovered by Newport in 185 1. 

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REGENERATION IN EGG AND EMBRYO 



217 



across the middle line, but whether the two phenomena are causally 
connected, or are merely due to a coincidence, could only be determined 
by further experiment. The observations themselves are not beyond 
question, for the two planes do not always coincide, and may be even 




Fig. 61. — After Roux. A. Section of semi-blastula of frog's egg. B. Half-embryo. C. Cross- 
section of last (reversed right and left in B and C). D, Anterior half-embryo. 

ninety degrees apart. These cases of divergence were thought by 
Roux to be due to an unobserved shifting of the developing embryo, 
but it is improbable that all cases can be accounted for in this way. 

Roux carried out his experiment by plunging a hot needle into 
one of the first two blastomeres, so that it is injured to such/aa extent 

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2l8 REGENERATION 

that its development is prevented. The same needle, without heating 
again, was used for one or two other eggs, for, if the needle had been 
so hot in the first instance that both blastomeres had been injured by 
the heat, this might not happen in the second or the third ^^g. It 
was found that amongst the eggs that had been operated upon in this 
way, some had been so much injured that neither blastomere developed, 
others had been so little injured that both blastomeres developed, but 
in the successful operations the uninjured blastomere developed, while 
the injured one did not. In the last case the uninjured blastomere 
divided, and produced a large number of cells. A segmentation 
cavity was present in the upper part of the hemisphere (Fig. 6i, ^). 
The injured half remained in contact with the other, completing the 
sphere, but it did not segment. A half-embryo developed from the 
uninjured half, as shown in Fig. 6i, B^ C. This embryo has a half- 
medullary fold along the side in contact with the injured half. At the 
anterior end somewhat more than half a head is present, and at the 
posterior end there is a half -blastopore. The cross-sections^ (Fig. 6i, 
C), through the embryo, show that beneath the half-medullary fold a 
rod-like notochord is present, which is made up apparently of fewer 
cells than the normal notochord, but it has, in cross-section, a round 
and not a half form. At the side, the mesoderm is present, as in the 
normal embryo, and it has produced the characteristic mesoblastic 
somites. An archenteron is formed in the half-embryo, and, since it 
is smaller than the normal, it may, perhaps, be called a half-archen- 
teron. The embryo is, therefore, in most respects a half -structure. 
The head is, however, nearly a whole head, but whether this is due 
to a whole head developing out of material derived entirely from one 
of the two blastomeres, or whether, as Roux supposes, a portion of 
the material of the injured blastomere has been worked over, i.e. 
"post-generated," remains, I think, an open question. 

The results of this experiment seem to confirm Roux*s conjecture 
that the material of each of the first two blastomeres is of such a sort 
that it gives rise to half the embryo, and, if so, there would be some 
probability that there is a causal connection between the first cleavage 
and the separating out of the parts of the embryo. In fact, Roux drew 
this conclusion, and even attempted to show how such a qualitative 
division is brought about. It should not be overlooked, however, that 
this conclusion goes beyond the legitimate bounds of deduction from 
the results, since the half-development takes place while the injured 
half retains its connection with the developing half, the former still 
remaining alive. On the other hand, the presence of the injured half 
makes the experiment more suitable to demonstrate that each of the 
first blastomeres gives rise, under normal circumstances, to half of the 

1 The cross-section C is reversed as compared with the half-cmbocp B, , 

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REGENERATION IN EGG AND EMBRYO 219 

embr}'o. If one half had been removed, we can foresee that its 
absence might lead to other complications that would affect the 
result. 

The most important outcome of this experiment is, I think, to show 
that a half -structure may develop by itself, i,e, that there is a certain 
amount of independent power of development in the parts of the egg. 

Roux also tried to show that if, after the second cleavage has been 
completed, the two blastomeres that lie on opposite sides of the first 
cleavage plane are killed by a hot needle, the remaining two produce 
either an anterior or a posterior half of an embryo. An embryo 
derived from the two " anterior " blastomeres is represented in Fig. 
61, D, The anterior half of the body is present. Posteriorly the 
half-embryo abuts against the injured half. It is possible, I think, 
that this embryo may represent the anterior half of a whole embryo 
of half size that has been prevented from closing in posteriorly by the 
mass of injured material of the undeveloped blastomere. Roux did 
not determine positively whether the two "posterior" blastomeres 
could give rise to posterior half-embryos ; one embryo in his opinion 
appeared to bear out this interpretation. This part of Roux's work 
is, it seems to me, not so satisfactory as the part dealing with the 
first two blastomeres, and we may leave it, for the present, out of the 
discussion, and consider only the result of the first experiment, in 
which one of the first two blastomeres was injured. Since the prob- 
lems involved in the two cases are essentially the same, nothing will 
be lost by dealing with the first case alone. 

The uninjured blastomere first gives rise to a half-embryo. After 
this has been accomplished, other changes take place that " reorgan- 
ize," according to Roux, the material of the injured half in such a way 
that the missing half of the embryo is formed by a process that Roux 
calls "post-generation." This process can be studied only by means 
of sectioning the embryos, and since the eggs may be injured to a 
varying extent, there must be some uncertainty in making out the 
sequence of. events. It is found that the yolk of the injured blasto- 
mere is vacuolated in places, and that the protoplasm in the path of 
the needle has been killed (Fig. 61, A). Irregular pieces of chromatin 
are found in the protoplasm, which seem to come from an irregular 
breaking up of the nucleus. 

The changes that lead to the reorganization of the injured half 
may take place at different times in different eggs. Roux describes 
three kinds of reorganization phenomena. The first includes the 
formation of new cells in the injured half. Nuclei, surrounded by 
finely granular protoplasm, appear in the protoplasm of the injured 
blastomere. These nuclei arise from two sources : in part from the 
scattered chromatin of the injured blastomere itself, and in part from 

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220 REGENERATION 

nuclei, or from cells without walls that have emigrated from the 
developing half. Around these nuclei, as centres, the protoplasm 
(with its contained yolk) of the injured half breaks up into cells. This 
cellulation of the yolk may take place in different eggs at different 
times. In some cases it may not have appeared as late as the gas- 
trula stage of the uninjured half; in others, it may take place at the 
time when the uninjured half is segmenting.^ The formation of the 
cells in the injured half begins always near the developing half, and 
extends thence into the injured parts. The new cells are of different 
sizes, but are larger than those of the uninjured half. 

The cellulation of the yolk takes place only in the least injured 
parts of the protoplasm. Where the protoplasm and yolk have been 
much injured, they are changed over by the second method of reor- 
ganization. This part of the blastomere is either actually devoured 
by wandering cells, or is slowly changed under the influence of the 
neighboring cells, so that it becomes a part of these cells. 

The surface of the injured half is covered over by ectoderm that 
grows directly from the developing half (third method of reorganiza- 
tion), — at least this happens where the protoplasm has been much 
injured. In other parts of the injured half the new cells that have 
appeared in this part, and that lie at the surface, become new 
ectoderm. 

Post-generation now begins in the reorganized and cellulated 
half; the cells become changed over into the different layers and 
organs that make the new half-embryo. A few hours or a night is 
sometimes sufficient to change a hemi-embryo into a whole embryo. 
The new half-medullary fold develops from the new ectoderm to 
supplement the half already present. The mesoblast appears over 
the side. Its upper part seems to come from the uninjured meso- 
derm that has grown over to the other side, but this is added to at the 
free edge by cells that belong to the newly cellulated part. The new 
differentiation is, in general, in a dorso-ventral direction. The lack- 
ing half of the archenteron arises in connection with the half of the 
archenteron already present in the hemi-embryo. The yolk cells 
arrange themselves radially, and a split appears in the post-gen- 
erated part, extending from the archenteron of the hemi-embryo. 
The split opens, and the new half-archenteron appears. In general, 
Roux states, the post-generation of the organs of the injured half 
proceeds from the already differentiated germ-layers of the hemi- 
embryo. The post-generation begins where the exposed surfaces of 
the germ-layers of the hemi-embryo touch the newly cellulated regions 
of the injured half. 

^This difference is due, I suppose, to the amount of injury that the nucleus of the 
injured half may have suffered. 



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REGENERATION IN EGG AND EMBRYO 221 

It is most difficult to account for these post-generative changes, 
since the new part has, according to Roux, a double and even a three- 
fold origin. The pieces of the old nucleus, he admits, may take a part 
in the formation of the new cells; wandering cells migrate from the 
yolk mass of the old half into the new, and the cells of the formed 
germ-layers may be pushed over to the other side. Since a certain 
share, and perhaps a large share, of the new cells comes from the 
hemi-embryo, it is clear that, in addition to the power of self-differen- 
tiation shown by the uninjured blastomere, we must also ascribe to it 
certain regenerative powers, at least to the extent that each kind of 
cell that comes from it can give rise in the injured half to cells like 
itself, and produce similar structures in the other half. 

If then, as Roux supposes, the development of the egg consists in 
an orderly, qualitative series of changes that lead to the subsequent 
differentiation, we must also suppose that the new parts are gifted 
with latent powers by virtue of which they can re-create all parts of 
the other half. Roux supposes, in fact, that each cell carries with it 
a sort of reserve-plasm, that is dormant in ordinary development but 
is awakened when any disturbance of the normal development takes 
place. Objections have been made to this subsidiary hypothesis, 
since the addition of this to the original assumption of a series of 
qualitative changes involves such complications that the view can 
hardly be considered a probable one. This objection is, I think, not 
as strong as certain critics believe, since the facts of development 
show beyond a doubt that although the egg has the power of pro- 
gressive change it has also, as certain experiments show, the power 
of reorganization, if the ordinary course of events is interrupted. 
This admission by no means throws us back upon Roux's hypothesis, 
for, as will be shown later, a different conception of the development 
may better account for both phenomena. 

Inasmuch as a good deal of discussion has taken place in regard 
to the process of post-generation described by Roux, it should be 
stated that Endres and Walter reexamined the process, and found, as 
had Roux, that the reorganizing cells migrate from the uninjured to 
the injured side, and around them the protoplasm of that side makes 
new cells. They found that the injured half is directly overgrown 
by the ectoderm from the developing half. When the material of the 
injured blastomere is only incompletely reorganized, there is formed, 
after post-generation, an embryo that has a protrusion of yolk in the 
dorsal part of the body. When the injured material is completely 
worked over, a perfectly formed embryo may result. The typical 
half-embryos that Roux obtained were also obtained by Endres and 
Walter. They deny that whole embryos develop from one of the 
first two blastomeres, as Hertwig affirms. ^ , 

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222 



REGENERATION 



Hertwig repeated Roux*s experiment and obtained results entirely 
different from those of Roux. He injured one of the first two blasto- 
meres of the frog's ^^ig with a hot needle, or by means of a galvanic 
current. Hertwig states that after the operation the egg turns so 
that the uninjured part lies uppermost. This is owing, he thinks, to 
the appearance of a blastula or of a gastrula cavity in the developing 








# 





Fig. 62. — After O. Hertwig. A. Section through a frog's egg (blastula stage) in which one blasto- 
mere had been killed. B. Same. Gastrula stage. C. I^ter gastrula stage. A E. Surface 
view of embryos from one of first two blastomeres. F. Same as last (^). Dorsal view. 
G. V'eniral view of last //. Dorsal view of another embryo, lying in a very eccentric position. 
/. Later stage of embryo from one blastomere. Other injured blastomere nearly covered 
over. J. Section through gastrula st.ige of embryo from one of first two blastomeres. 
K. Cross-section of the embryo shown in F and G. 

part. The segmentation cavity is found in many cases surrounded by 
the cells of the segmenting half (Fig. 62, A\ but at other times at the 
border between the new and the old parts. In still other cases the 
cavity may lie eccentrically, and in some cases the floor of the cavity 
may be bounded by the yolk substance of the injured half. An em- 
bryo appears on the upper, uninjured part, though it is not, according to 
Hertwig, a half-embryo, but a whole embryo, or at least oiie approach- 
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REGENERATION IN EGG AND EMBRYO 223 

ing that condition (Fig. 62, D, E, F, Gy H), It is shorter than the 
normal embryo, and its posterior end is incomplete. When these 
embryos are cut into sections, it is found that the part that has 
developed corresponds to the dorsal part of a normal embryo, but 
the ventral part is continuous with the yolk substance of the injured 
half (Fig. 62, By C, y, K), Hertwig interprets these embryos as 
forms in which the yolk portion of the developing half, together with 
the whole of the injured blastomere, represents a yolk mass that has 
not yet been enclosed by the margin of the developing part. 

In nearly all the embryos that Hertwig has described, the medul- 
lary folds appear eccentrically on the developing half (Fig. 62, D, /% 
K)y and in some cases they may lie so far to one side that they are 
situated almost at the edge ; and the less development of one of the 
folds makes the embryo appear almost like the hemi-embryos obtained 
by Roux. In fact, one embryo seems to have been a true hemi- 
embryo. 

Hertwig attributes the eccentric position of the embryo to the 
eccentric position of the blastopore of an earlier stage, but he does not 
attempt to account for the eccentricity of the latter. 

It is significant in this connection to find that Hertwig obtained 
other embryos that show a condition of " spina bifida." In these 
there is an exposure of yolk in the mid-dorsal line between the halves 
of the medullary folds. Still other embryos in the same series of 
experiments were only slightly injured, and developed nearly nor- 
mally. In these cases, Hertwig thinks, the blastomere that was 
stuck had been only slightly injured, and had partly developed. I 
have also often observed in this experiment that the injured blasto- 
mere may segment and add cells to the developing half, but in such 
cases the development of the injured half may be less regular than is 
that of the uninjured half. It seems to me not improbable that in sev- 
eral of the embryos described by Hertwig both blastomeres have taken 
part in the development. The main points of difference between 
the results of Roux and of Hertwig cannot, however, be explained 
in this way, and the explanation is to be found in another direction. 

Hertwig emphasizes the view that the injured blastomere is not 
dead, but exerts an influence upon the other half — an influence of 
the same kind as that which the yolk of a meroblastic tgg has on the 
protoplasmic portion of the tgg from which the embryo arises. He 
ventured to prophesy that if the injured yolk mass could be entirely 
removed, the uninjured blastomere would produce a normal embryo 
without defect, and one like the normal embryo in every respect 
except in size.^ 

1 The development of isolated blastomeres of the ctenophore egg shows that this need 
not be the case. 



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224 



KECENERA TION 



Roux interprets Hertwig*s results as due to the sudden partial 
post-generation of a part of the injured half of the egg. He thinks 
that a half-embryo had first developed, and then to this there has been 










Fig. 63. — A. After Wetzel. Section through an egg (blastula stage) reversed at two-celled stage. 

B. After Schultze. Double embryo, from reversed two-celled stage, united ventrally. 

C, C^. Two views of another double embryo (united dorsal ly). C^. Cross-section through 
last. D, After Wetzel, Double embryo united laterally. D^. Section through same. 



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REGENERATION IN EGG AND EMBRYO 225 

quickly added a part of the missing side. This reply fails, however, 
to meet Hertwig's description of the method of development of the 
embryos. Later work, however, has put us in a position to give a 
more satisfactory account of the differences between the results of 
Roux and Hertwig. It seemed to me that the two kinds of embrj^os 
might be due to the different positions of the eggs after the operation. 
It had been shown by Schultze ('94) that if a normal egg in the two- 
celled stage is turned upside down and held in that position two 
embryos develop from the egg (Fig. 63, By C, D). These embryos 
are united in various ways, and arise presumably one from each of 
the first two blastomeres. These results have been confirmed by 
Wetzel, who examined more fully into the early development of the 
twin embryos. He showed with much probability that the proto- 
plasm rotates in each blastomere, so that in many cases the lighter 
part flows, or starts to flow, toward the upper hemisphere of the egg. 
In this way similar protoplasmic regions of the two blastomeres 
may become separated, and under these circumstances each blasto- 
mere gives rise to a whole embryo. A cross-section through one of 
the segmentation stages of one of these eggs is shown in Fig. 63, -^. 
The smallest cells are found at the outer side of each half, and the 
two segmentation cavities lie one in the upper region of each hemi- 
sphere. Some of the different kinds of embryos that develop from 
inverted eggs are shown in Fig. 63, B, C, D, They are united in Fig, 
63, B, by their ventral surfaces, and in Fig. 63, C, C^ C^ by their 
dorsal surfaces, and in Fig. 63, D, D ^, at the sides. These differences 
are probably accounted for by the different ways in which the proto- 
plasm of the first two blastomeres rotated before the egg divided. 

A consideration of these results led me to carry out the following 
experiment on eggs operated upon by Roux's method. After stick- 
ing one of the first two blastomeres, some of the eggs were placed 
so that the uninjured blastomere kept its normal position, i,e, with 
the black hemisphere upward. Other eggs were turned, so that 
more or less of the white hemisphere was upward. From the two 
kinds of eggs two kinds of embryos were obtained. From those with 
the black hemisphere upward the embryo was a half-embryo like that 
described by Roux, while from the eggs with the white hemisphere 
upward embryos developed that were in many respects whole embryos 
of half size.^ The explanation of this difference will be 'obvious from 
what has been said. When the black hemisphere is uppermost the 
contents of the uninjured blastomere remain as in the normal ^%gy 
and a half-embryo results. When the white hemisphere is uppermost 
the contents of the uninjured blastomere rotate, so that it generally 
shifts its relation to the protoplasm in the other injured half, and a 

^ In one case a half-embryo resulted. 

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226 REGENERATION 

whole embryo develops, as in Schultze's experiment. In one case I 
obtained a half-embryo from an inverted egg. The result did not 
appear to be due to a lack of rotation of the protoplasm, because the 
medullary folds were white, showing that the protoplasm must have 
changed its position. The result can possibly be explained as due 
to the protoplasm rotating in each blastomere along the line between 
the halves, so that it still retains the same relation as that of the 
normal two-celled stage. 

The whole embryos of half size are generally imperfect in certain 
respects on account of their union with the other half. They resemble 
in all important points the embryos described by Hertwig, and I see 
no grounds for interpreting them as embryos of a meroblastic type, 
but rather as whole embryos of half size, whose development pos- 
teriorly and ventrally has been delayed or interfered with by the 
presence of the other blastomere. 

It has not been possible to separate the first two blastomeres of 
the frog's egg, for if one is removed the other collapses. In the sala- 
mander, that has a mode of development similar to that of the frog,^ 
it has been possible to separate the first two blastomeres. Herlitzka, 
who carried out this experiment, found that each blastomere gives rise 
to a perfect, whole embryo of half size. We cannot doubt, I think, 
that the same power of producing a whole embryo is also present in 
each of the first two blastomeres of the frog's egg. When the two 
remain in contact in their normal relation to each other, each produces 
only a half ; when like regions of the two blastomeres are separated, 
each produces a whole embryo. Thus we see that whatever the fac- 
tors may be that determine the development of a single embryo from 
the egg, still each half, and perhaps each fourth also, has the power of 
producing a whole embryo. 

In later papers Roux has stated that he had also, even in his 
earlier experiments, found other kinds of embryos than the half -em- 
bryos that he described. Some of these were whole embryos that 
had developed from the uninjured blastomere without the injured one 
taking any part or only a very small share in their formation. He 
found, he states, all stages between those embryos that had used up 
all the yolk material of the injured side (though post-generated) and 
those that had not used any part of it. The latter kind of embryo he 
does not recognize as a whole embryo of half size in the sense that a 
single blastomere has developed directly into a smaller whole embryo, 
but he believes that there must have been formed at first a half-blas- 
tula, half-gastrula, half-embryo, and that the last stage completed 
itself laterally without using any material from the injured half. 

^ The plane of the first cleavage has been shown in two urodeles to correspond, not to the 
median longitudinal plane, but to a cross-plane of the embryo. 



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REGENERATION IN EGG AND EMBRYO 22/ 

That the uninjured blastomere may at first segment as a half is not 
improbable, but that whole embryos are formed only by the formation 
of new material at the side of a half-embryo is, I think, hardly possible, 
since the results of Schultze, Wetzel, Hertwig, and myself show that 
a whole embryo may develop directly out of the material of a single 
blastomere. 

Spemann (1900) has carried out some novel experiments on the 
eggs of triton, and has shown how in another way double structures 
may be produced. If a ligature is tied loosely around the egg at 
the first cleavage exactly along the division plane between the first 
two blastomeres, it will be found later that the long axis of the single 
embryo lies, in the great majority of cases, across the ligature, and 
only in a small percentage of cases does the median plane correspond 
with that of the ligature, and, therefore, with the first cleavage plane. 

If one of the latter eggs is allowed to develop to the blastula 
stage, and the ligature is then drawn tighter, so that the blastula 
is completely constricted, an embryo develops from each half. 

If one of the former eggs is allowed to develop to a stage when the 
medullary plate is laid down, but is not yet sharply marked off, and 
the ligature is then tightened, there will be formed (the plane of con- 
striction being across the medullary plate) from the anterior part a 
normal head with eyes, nasal pits, ears, and a piece of the notochord, 
and from the posterior part there will be formed, at its anterior end, 
another new head just behind the ligature. Ear-vesicles develop in 
this part at the typical distance from the anterior end. The brain 
that develops has a typical cervical curvature, and eye evaginations 
appear at the anterior end. The chorda, that extended at first to the 
anterior end of this region, is partially absorbed. 

If the ligature is drawn tighter at a later stage, when, for instance, 
the medullary plate is plainly visible but is still wide open, a different 
result is obtained. The posterior part no longer forms a new head at 
its anterior end, but develops into those structures that it would form 
normally. In some cases it was found that the region from which 
the ear develops had been pinched in two, and in consequence a 
small vesicle appears in front of the constriction and another behind it. 

In those cases in which the ligature lies in the median plane of the 
embryo, it is found that a double anterior end is produced. As the 
embryo develops it tends to elongate, and in consequence the mate- 
rial is pushed forward on each side of the ligature. A double head is 
the result. The extent of the doubling depends on the depth of the 
constriction between the halves. In the most extreme cases two com- 
plete heads are formed with an inner nasal pit, eye, and ear on each 
head, as well as the normal outer ones. The results show that even 
such complicated structures as the eyes and ears, etc., may arise 

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228 



REGENERATION 



from parts of the body where they never appear under normal 
conditions. 

A series of experiments that have been made on the eggs of sea- 
urchins has led to equally important results. The earliest experi- 
ments are those of O. and R. Hertwig, who, in addition to studying 
the effect of different drugs on the developing egg, found that 
fragments of the eggs of sea-urchins, obtained by violently shak- 
ing the eggs in a small vial, could give rise, if they contained a 




Fig. 64. — Sea-urchin egg and embryo. A. Two-cell stage. B. Same, with blastomeres separated. 
G. Two half-sixteen-cell stages. C. Open half-blastula stages. D. One of last, later stage, 
closed blastula of half size. E, Gastrula of half size. F. Whole pluteiis of half size. H. A 
hall-sixteen cell dividing in same way as a whole egg (eight cell) . /. Whole egg at sixteen- 
cell stage. 

nucleus, to small whole embryos. Boveri made the important discov- 
ery in 1889 that if a non-nucleated piece of the ^^g of the sea-urchin 
is entered by a single spermatozoon, the piece develops into a whole 
embryo of a size corresponding to that of the piece. Fiedler, in 1891, 
separated the first two blastomeres by means of a knife, and found 
that the isolated blastomere divides as a half, but he did not succeed 
in obtaining embryos from the halves. Driesch has made many ex- 
periments, beginning in 1891, with the eggs and embryos of the sea- 
urchin. He separated the first two blastomeres (*9i) by means of 

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REGENERATION IN EGG AND EMBRYO 229 

Hertwig's method of shaking the eggs, and studied the development 
of the isolated blastomeres. He found that the cleavage was strictly 
that of a half, and not like that of a whole egg. The normal egg 
divides into two, four, and eight equal parts. At the next division, four 
of the cells divide very unequally, producing four very small cells, 
the micromeres, at one pole. The four cells of the other hemisphere 
divide equally (Fig. 64, /). The isolated blastomere divides at first 
into two equal parts, then again into equal parts. At the next divi- 
sion two of the cells produce micromeres and two divide equally (Fig. 
64, G\ This is exactly what happens at this division in each half, if 
the blastomeres are not separated. In later stages a half -sphere is 
formed that is equivalent to half of the normal sphere (Fig. 64, C), 
The open side corresponds to the side at which the half would have 
been united to the other half. Thus up to this point a half-cleavage 
and a half-blastula have appeared.^ 

In later stages the open half-blastulae close in, producing a whole 
sphere that becomes perfectly symmetrical (Fig. 64, Dy A symmetri- 
cal gastrula develops (Fig. 64, ^) by the invagination of a tube at one 
pole, and a symmetrical embryo is formed (Fig. 64, F^ that resembles 
the normal embryo except in point of size. 

Driesch has also found that a number of twin embryos arise from 
the shaken eggs. They arise from eggs whose blastomeres have been 
disturbed or shifted, so that each produces a small whole embryo, the 
two embryos being united to each other in various ways. 

In a second paper, published in the following year, Driesch ex- 
tended his experiments, and attempted to discover how far the " inde- 
pendence " of the blastomeres extends ; i.e, he tried to find out if all 
the blastomeres resulting from the cleavage are alike. When one 
of the first four cells is separated from its fellows by shaking, it 
continues to divide, in most cases as a quarter, and produces later 
a small spherical blastula. Many of these blastulae, although 
apparently healthy, never develop further, although they may remain 
alive for several days. In one experiment only eight out of twenty- 
six reached the pluteus stage, with a typical digestive tract and 
skeleton. 

From these experiments Driesch drew the important conclusion 
that the cleavage cells or blastomeres of the sea-urchin's Q,gg are 
equivalent, in the sense that if they were interchanged a normal em- 
bryo would still result. A somewhat similar view is expressed in the 
dictum that the position of a blastomere in its relation to the others 
determines what part it will produce, if its position is changed it 
gives rise to another part, etc., — or, expressed more concisely, the 

^ In some cases, especially in sph?erechinus, even at the eight-celled stage, the blasto- 
meres seem to shift their position, so that a whole sphere of half size is formed. 



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230 REGENERA TION 

prospective value of a blastomere is a function of its position.^ 
Driesch extended these experiments further in 1893. His aim was 
to separate different groups of cells at the sixteen-cell stage in order 
to see whether the cells around the micromere pole (or "animal pole '*) 
if separated from those of the opposite (or "vegetative pole") could 
produce a whole embryo, etc. Eggs whose membranes had been re- 
moved by shaking immediately after fertilization were allowed to 
develop normally to the sixteen-cell stage and were then shaken into 
pieces. Amongst the groups of cells that were present those that con- 
tained the micromeres were picked out. It was found that they give 
rise to whole embryos. In order to obtain cells that belong to the 
vegetative hemisphere, the blastomeres were shaken apart at the 
eight-cell stage, and those groups of cells that in later divisions did 
not produce micromeres were isolated. From these also whole em- 
bryos develop. The results show that the cells of both hemispheres 
are able to produce whole embryos, and that at the sixteen-cell stage 
the different parts of the egg are still capable of producing all parts 
of the embryo. It is important to observe that the results of the 
experiment do not show that if the normal development goes on 
undisturbed any part of the tgg may become any part of the em- 
bryo, for it is highly probable that a definite region of the egg may 
always produce a definite part of the embryo. The results do show, 
however, that, even if this is true, any cell has the power of produc- 
ing any or all parts of the embryo if the normal conditions are 
changed. 

In connection with these experiments Driesch discussed the fac- 
tors that determine the axial relations of the embryo. If all the cells 
have the power of producing all parts, what determines in the normal 
development, and also in the development of a part of the whole, the 
axial relations of the embryo f Driesch assumed that the egg has a 
polar structure, and that the same polarity is found in all parts of the 
protoplasm. Around this primary axis all the parts are alike or 
isotropous.^ The origin of the mesenchyme and the position of the 
archenteron, that develop at one pole, are determined by the polarity 
of the protoplasm. The plane of bilateral symmetry may appear in 
any one of all the possible radial planes around the primary axis. 
The selection of a particular one is due to some accidental difference 
in the structure of the protoplasm, or to some external factor. In 
later papers Driesch modified this view, and assumed that along with 
the primary polarity a bilateral structure also exists in the proto- 
plasm. 

^ Hertwig had a year before expressed a similar view in regard to the equivalency of the 
blastomeres. 

* A view advanced by Pfliiger. 



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REGENERATION IN EGG AND EMBRYO 23 1 

Wilson ('93) Studied the development of isolated blastomeres of 
amphioxus, and found that it agreed in all essential respects with 
the mode of development of the blastomeres of the sea-urchin. The 
isolated blastomeres of the two-cell and four-cell stages produce whole 
embryos, but the blastomeres of the eight-cell stage develop only 
as far as the blastula. The blastomeres segment, after separation, 
in most cases not as a part, but as a whole ^^g would divide, 
although the cleavage of the one-eighth blastomere only approaches 
that of the entire egg, but is never identical with it. Incompletely 
separated blastomeres give rise to twins, triplets, etc. Wilson agreed 
with the Hertwig-Driesch conception of the value of the early blasto- 
meres, and accepted the view that the fate of each is a function of 
its position, and that at first they are qualitatively alike. During the 
early cleavage he supposed that a change takes place that is slight 
at the two-cell stage, greater at the four-cell stage, and in the eight- 
cell stage the differentiation has gone so far that the blastomere can 
no longer return to the condition of the ovum. "The ontogeny 
assumes more and more the character of a mosaic work as it goes 
forward." 

Loeb ('94) showed that if the eggs of the sea-urchin are placed in 
sea water, diluted by distilled water, the tgg swells and bursts its 
membrane, so that a part of its protoplasm protrudes. Into this pro- 
trusion some of the first-formed nuclei pass, and from both the part 
remaining in the egg membrane, as well as from the protruding part, 
an embryo is produced, the two embryos often sticking together. In 
several cases two to eight separate groups of blastomeres are formed 
from one egg and develop into whole embryos.^ 

The question of the number of cells which are produced by the one- 
half and one-fourth embryos had not up to this time been determined. 
Until this was known it could not be stated whether the smaller 
embryos were miniature copies of the normal embryos in all respects, 
or whether they assumed the typical form with fewer cells. I found 
('95) that the blastula from one of the first two blastomeres contains 
half the number of cells produced by the whole embryo, and that in 
the later stages also it contains only about half the normal number. 
The one-fourth blastomere produces only a fourth of the whole num- 
ber of cells, and yet can develop with this number, in many cases, 
into a whole embryo. The one-eighth blastomere produces one- 
eighth the normal number of cells. In most cases I found that these 
one-eighth blastomeres do not produce embryos, but occasionally 
they produce a gastrula, and probably a young pluteus stage. 

1 The evidence to show that more than four and certainly more than eight such groups 
that come from a single egg can produce a pluteus is, I think, insufficient, and the result 
improbable. ^ t 

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232 REGENERATION 

The development of nucleated fragments of the egg was also 
studied in order to find out if they too produce a smaller number of 
cells than does the whole ^^'g, and a number in proportion to their 
size. The problem is different in this case, because the nucleus has 
not divided before the piece is separated, and the results ought to 
show whether there is a prescribed number of divisions for the egg 
nucleus, or whether the number of times it divides is regulated by 
the amount of the protoplasm. It was found that the number of 
cells produced by each fragment is in proportion to the size of the 
piece. This shows that the division of the nucleus is brought to an 
end when the protoplasm has become subdivided to a certain point. 

A further examination of the number of cells that are invaginated 
in these smaller " partial " larvae to produce the archenteron seemed 
to show that they often use relatively more than their proportionate 
number. The normal blastula of Sphcerecliinns granulans contains 
about five hundred cells and turns in fifty cells, or one-tenth the total 
number. The one-half and one-fourth embryos, and some of the 
small embryos from the egg fragments, seemed to invaginate more 
than one-tenth of their total number of cells. 

Driesch (1900) reexamined this point, and found that the em- 
bryos from isolated blastomeres may use the proportionate number 
of cells. I have made a new study of the problem on a larger scale 
and have found that my earlier statement, as well as that of Driesch, 
is substantially correct, and that the difference that we found is due 
to the time at which the embryos gastri^late. Thus the one-half 
embryos and even the one-fourth embryos, that gastrulate as soon as 
(or only a little later than) the normal, whole embryos, turn into the 
archenteron about one-half and one-fourth the number of cells 
invaginated in the whole embryo ; but those partial embryos that 
gastrulate later (as most of theiji do) turn into the archenteron more 
than a half or a fourth of the number of cells turned in at first 
by the whole embryo. This difference between the early and the 
retarded partial embryos is in large part due to a slow increase of 
cells that takes place during the delay in development. 

Driesch ('95) found that pieces of the blastula wall of the sea- 
urchin, if large enoughy can also produce a gastrula and embryo. I 
found that the number of cells in these pieces does not increase 
appreciably after they are cut off (if the operation has been carried 
out at the end of the cleavage period), and that the new embryo is 
organized out of the cells present at the time of removal of the piece 
from the wall. There is, therefore, in this case no chance for " post- 
generation " by means of new cells produced at the side, which Roux 
has supposed to take place in the frog embryo. 

The development of pieces of the blastula wall, if thejr are not too 

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REGENERATION IN EGG AND EMBRYO 233 

small, also shows that the lack of power to develop, found in some 
of the one-fourth and in many of the one-eighth blastulae, is not 
the result of any special differentiation that they have undergone 
during the cleavage period, but is due to their size. 

A recent series of experiments by Driesch (1900) on the develop- 
ment of isolated blastomeres of the sea-urchin's egg has given more 
exact data in regard to their limit of power to produce embryos, and 
has shown the possibilities in these respects of different parts of the 
egg. By means of a method discovered by Herbst (1900) it is pos- 
sible to obtain isolated blastomeres more readily than by the some- 
what crude shaking process. If the eggs, after fertilization and after 
the removal of the membrane by shaking, are placed in an artificial 
sea water, from which all calcium salts have been left out, the eggs 
divide normally, but the blastomeres are not held firmly together, and 
readily fall apart if the egg is disturbed. By means of a fine pipette 
any desired blastomere or group of blastomeres can be picked out. 
If these are returned to sea water they continue to develop. 

Driesch found that the one-half and one-fourth blastomeres 
develop into proportionate gastrulae and larvae ; that the one-eighth 
blastomeres, both of the animal and the vegetative hemispheres, some- 
times produce gastrulae, and even the beginning of the larval stage 
with the rudiments of a skeleton. There are certain differences 
between the one-eighth larvae that come from the animal hemisphere 
and those from the vegetative half. More of the one-eighth 
blastomeres from the animal part of the Q^g die than from the 
opposite part, but of those that remain alive a larger percentage 
reach the gastrula stage than in the case of those from the vege- 
tative pole ; their protoplasm moreover is not so clear as is that of 
the larvae from the other hemisphere. These "animal pole" blasto- 
meres develop faster than those of the other sort. The gastrulae 
from the one-eighth blastomeres o'f the vegetative hemisphere do 
not die so often after separation, the protoplasm of the larvae is 
clearer, and they often produce long-lived blastulae with long cilia. 
The blastulae often develop into gastrulae without mesenchyme. 
These results show that although whole larvae may be produced from 
the one-eighth blastomeres of both hemispheres, yet there are certain 
characteristics that may be referred with great probability to differences 
that are present in the protoplasm of the two hemispheres of the egg. 
The differences are not in all cases sufficient to interfere with the 
production of all the characteristic structures of the embryo, yet 
traces of the origin of the larvae can be found in their structure. It 
is probable that the so-called animal (or micromere) pole corresponds 
to that part of the egg from which the archenteron is produced. 
Hence the one-eighth blastulae from this hemisphere gastrulate 

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234 REGENERATION 

sooner and in proportionately larger numbers than do those from the 
opposite hemisphere. The vegetative hemisphere would correspond 
to that part of the ^%% from which the wall of the normal gastrula is 
derived, and this may account for the clearer protoplasm of these 
embryos, their inability in many cases to gastrulate, their larger cilia, 
and the absence of mesenchyme in some of them. Driesch finds 
that the number of cells' that go into the mesenchyme of the partial 
larvae is in proportion to the total number, and that the number of 
cells in the archenteron is probably also proportionate.^ 

The smallest blastomeres that produce gastrulae are the one- 
sixteenth products. Out of a total of 139 cases only 31 produced true 
gastrulae, 5 produced gastrulae with evaginated archenteron, and 103 
remained blastulae with long cilia. The one-thirty-second blasto- 
meres were not observed to gastrulate. 

Driesch ('95) has also made a study of the potentialities of the 
blastula and gastrula stages of sphaerechinus, echinus, and asterias. 
If a blastula is cut in half before the mesenchyme cells are produced, 
both pieces produce gastrulae and larvae. Since some of the pieces 
probably come from the animal hemisphere, and others from the vege- 
tative hemisphere, it follows that all parts of the blastula possess the 
power of producing whole embryos, and in this respect the potentiali- 
ties are the same as for the blastomeres. If the experiment is made 
at a stage just before the archenteron has begun to develop (Fig. 65, 
A), the results may be different. A half that contains the region 
from which the archenteron is about to develop will produce a gastrula 
and a larva (Fig. 65, A, lower row to right of -^). A half that contains 
only the opposite regions of the egg (Fig. 65, Ay upper row) may in 
some cases gastrulate,'-^ often abnormally, but as many as half of the 
pieces do not gastrulate. They may remain alive for a week or more, 
and even produce a typical ciliated ring with a mouth in the centre, 
but do not form a new archenteron. These important results show 
that after the formation of the mesenchyme and archenteron at one 
pole, the other cells of the blastula wall are no longer able to carry 
out a process that the same cells were able to carry out at a slightly 
younger stage, but whether this loss of power is connected with the 
previous formation of the archenteron, or due to some other change 
which has by this time taken place in the cells, cannot be determined 
from the experiment. It is also important to note that these small 
ectodermal blastulae can still develop whole, typical, ectodermal 
organs, the ciliated ring and the mouth, and that the former especially 
has the characteristic structure of the whole normal ring. 

^ Driesch's figures seem to show, nevertheless, that the archenterons are proportionately 
too large. 

2 These may be pieces that were cut obliquely, as Driesch suggests, so that they con- 
tain a part of the archenteric region. 

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REGENERATION IN EGG AND EMBRYO 



235 



Similar phenomena have been made out by Driesch in the devel- 
opment of the archenteron of the same forms. At the end of the nor- 




© V 





o o 



Fig. 65. — A. Blastula of sea-urchin beginning to gastrulaie. Cut in half as indicated by line. 
Two rows of figures to right show development of upper and lower halves. B. Later gastrula 
cut in half. Two rows of figures to right show lati*r development. C. End of gastrulation 
process. Embryo cut in half. Two rows of figures to right show later stages of eaclf half. 
D, Formation of endodernial pouches from inner end of archenteron. Embryo cut in two. 
Two rows of figures to right show later stages. 

mal gastrula period of the starfish embryo, there is produced from the 
inner part of the archenteron two outgrowths, or pouches, that later 
constrict off to give rise to the coelom sac and water-vascular^^stem.^ 

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236 REGENERA TION 

If the gastrula is cut in two in such a way that the inner end of the 
archenteron, ue, the part from which the pouches develop, is cut off 
(Fig. 65, C\ it is found that the piece containing the posterior part 
of the archenteron closes in, forms a new sphere, and from the present 
inner end of the archenteron (that has also healed over) a pair of 
pouches is produced (Fig. 65, C, lower row to right of C\ These 
pouches have arisen, therefore, from a more posterior part of the 
archenteron than that from which the pouches normally arise. 

If the same experiment is made at a later stage, when the pouches 
have been given off from the archenteron (Fig. 65, -D, lower row to 
right of D\ no new pouches are formed. This means that after the 
archenteron has once produced its pouches it loses throughout all its 
parts the power to repeat the process, although these parts possessed 
this power at an earlier stage. It is a very plausible view that the 
result is directly connected with the formation of the normal pouches, 
although it is of course possible that some other change has tak^n 
place in the archenteron that prevents the formation of the pouches. 

In order to give as nearly as possible a consecutive account of the 
experiments on the eggs of the frog and of the sea-urchin, a number 
of other discoveries have been passed over. Let us now examine 
some of the results on other forms. 

Chabry, as early as 1887, experimented with the eggs of an ascid- 
ian. By means of an ingenious instrument he was able to prick and 
kill individual blastomeres. The results of his experiments were not 
described very clearly, and later writers have interpreted his results in 
different ways.^ Chabry stated that he obtained half-embryos from 
one of the first two blastomeres, but his figures show, especially in 
the light of later work, that the embryos were whole embryos of half 
size, although certain organs, as the papillae and the otolith, may be 
lacking. 

Driesch ('95) reexamined the development of isolated blastomeres 
in one of the ascidians, Phalliisia mammalata^ and found that the 
cleavage of blastomeres, isolated by shaking, is neither like that of 
the whole ^gg, nor is it like that of half the normal cleavage, although 
it shows some characteristics of the latter. A symmetrical gastrula 
is produced, and from this a typical whole larva of half size. These 
larvae lack, however, one or more papillae, and the otolith rarely 
develops. The absence of these organs Driesch ascribes to the 
rough treatment that the ^gg has received, since embryos from whole 
eggs may sometimes lack these organs if the development has taken 
place under unfavorable conditions. The isolated one-fourth blasto- 
mere may also produce a whole larva. 

Crampton ('97) has also studied the development of the isolated 

1 Driesch, Hertwig, Roux, Weismann, Barfurth. For review see Driesch ('qO.i 

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REGENERATION IN EGG AND EMBRYO 237 

blastomeres of another ascidian, Molgiila manhattensis. He has more 
fully worked out the cleavage, and finds that the isolated blastomere 
segments as a part, i.e. as it would have segmented had it remained 
in connection with the rest of the egg. In general appearance 
the half-cleavage seems to differ from the half of the complete 
cleavage, because rearrangements of the blastomeres occur, but 
despite these shiftings the form of the division is always like that of 
a part. A whole embryo develops, although there may be defects 
in certain organs, which are due, he suggests, to the smaller amount 
of material available for the development of the larva. 

Zoja showed in 1894-1895 in a number of jellyfish that the iso- 
lated blastomeres produce whole larvae of smaller size.^ In one form, 
liriope, the endoderm that forms the digestive tract is normally de- 
laminated at the sixteen-cell stage, each cell of the blastula wall 
dividing into an inner and an outer part. In the blastula from the 
one-half blastomere this delamination also takes place when sixteen 
cells are present, and not at the preceding cleavage when only eight 
cells are present. In this form, therefore, the whole number of cells 
develops before the delamination takes place, and the one-half larva 
is composed of the same number of cells as is the normal embryo at 
this stage, but the cells are only half as large. In other species the 
endoderm appears to begin to develop in the half-larvae when only 
half the total number of cells is present. 

The conditions in the egg of the bony fishes are very different 
from those in the preceding forms. The protoplasm, from which the 
embryo is produced, accumulates at one pole to make the blastodlsc. 
After the cleavage of this blastodisc, the blastoderm that has resulted 
grows over the yolk sphere at the same time that the embryo is form- 
ing along one meridian. I carried out some experiments, in 1895, 
on the eggs of Ftindtilus hcterocliUis. If one of the first two 
blastomeres of the egg of fundulus is destroyed, the remaining one 
produces a whole embryo. If three of the first four blastomeres are 
removed, the remaining one may produce a whole embryo of small 
size. The problem of development is, in the case of the fish, different 
from the other cases described, inasmuch as the whole yolk sphere is 
left attached to the remaining blastomere and is covered over by cells 
derived from this blastomere. The smaller embryo that is formed 
lies on a yolk of full size.^ 

Wilson's work on amphioxus has been already described in con- 

^ Bunting ('94) also found that isolated blastomeres of hydractinia make whole em- 
bryos. 

2 If the yolk of the dividing egg is partially withdrawn without disturbing the blasto- 
meres, the form of the cleavage may be altered, but a normal whole embryo develops over 
the smaller yolk sphere. ^->. j 

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238 



REGENER'ATION 



nection with the experiments on the sea-urchin's eggs. Later I ('96) 
also obtained whole larvae from one-half and one-fourth blastomeres, 
and I also found that the one-eighth blastomeres do not develop 
beyond the blastula stage. The number of cells of which the one- 
half larva is composed is half that of the normal larva, and the one- 




FlG. 66. — Ctenophore-egg and embryo. A. Normal sixteen-cell stage. B, Half-sixteen-ccll 
stage. C. I^ter half-segmentation stage. D. Later half-embryo. E. Corresponding whole 
embryo. F. Half-embryo seen from side. G. Same seen from apical end. In F and {/, 
four rows of paddles present, three endodermal sacs and ectodermal stomach. 

fourth larva is made up of one-fourth of the total number of cells. 
In all the preceding cases in which the blastomeres have been sepa- 
rated, a whole embryo has developed, although the cleavage was 
often like that of a part. In one form, however, it has been found 
that a whole embryo does not develop. Chun ('92) first showed that 
the isolated one-half blastomere of the ctenophore egg produced a 

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REGENERATION IN EGG AND EMBRYO 239 

half-larva. He also inferred from certain incomplete embryos caught 
in the sea, that these incomplete larvae could subsequently regener- 
ate the missing parts. Driesch and Morgan ('95) studied the devel- 
opment of the isolated blastomeres of another ctenophore, Bero'e ovata. 
They found that the isolated one-half blastomere divides exactly as a 
half of the whole egg (Fig. 66, A, By C\ It remains more or less a 
half -structure, even after the ectoderm has grown over the whole sur- 
face (Fig. 66, D\ The invagination of ectoderm, to form the so-called 
stomach, that takes place at the lower pole of the whole embryo, is 
formed at one side of the lower pole in the half -embryo (Fig. 66, F, G). 
It pushes into the endodermal yolk mass, and lies not in the middle, 
but somewhat to one side. In the normal embryo there are formed 
four endodermal sacs or pouches in the central yolk mass that become 
connected with the inner end of the ectodermal stomach, around 
which they lie symmetrically. In the half-embryo two sacs are 
formed, and in addition a smaller third sac, which always lies on the 
side of the stomach that is nearest the outer wall (Fig. 66, F, G), The 
embryo is, therefore, somewhat more than half the normal embryo in 
regard to the number of its endodermal sacs. 

There are present eight meridional rows of paddles in the normal 
embryos of the ctenophore. They lie symmetrically on the sides, 
converging towards an apical sense organ. In the one-half larva 
there are always only four of these rows of paddles that are not 
equally distributed over the surface, since on one side there is a wider 
gap between two of the rows than elsewhere (Fig! 66, G\ The 
sense plate also lies somewhat eccentrically, i.e. more towards the 
side corresponding to that at which the other blastomere lay. 

If the one-fourth blastomeres are separated, each continues to seg- 
ment as though still a part of the whole. A one-fourth embryo 
develops that has an unsymmetrical stomach, with two endodermal 
sacs. There are only two rows of paddles. The embryos are, there- 
fore, in several respects one-fourth embryos, but the presence of two 
endodermal sacs, instead of only one, shows that in this particular, 
at least, the embryo is more than a fourth of the whole. 

The part of the work of Driesch and Morgan, that has a special 
bearing on the interpretation of the one-half and one-fourth develop- 
ment of the isolated blastomeres, is that in which some experiments 
are described which consisted in cutting ofF portions of the unseg- 
mented egg. If a fertilized but unsegmented Qgg is cut in two by 
means of a small pair of scissors, the part that contains the nucleus 
may segment, and give rise to an embryo. The division is generally 
like that of a part, and in such cases an incomplete embryo develops. 
The embryo may have fewer rows of swim-plates than has the normal 
embryo, and fewer endodermal sacs, and the stomach may be in an 

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240 REGENERATION 

eccentric position. The embryos resemble in every respect the incom- 
plete embryos from isolated blastomeres. It is important to note that 
although the embryos from isolated blastomeres resemble those from 
pieces of the segmented ^%;g^ in the former case the nucleus has 
divided once, and each blastomere contains half of the original 
nucleus, while in the latter case the entire segmentation nucleus is 
present in the piece. These facts seem to show that in this egg the 
incomplete development is directly connected with the protoplasm, 
and not with the nucleus, — a view that is maintained by Driesch and 
Morgan in connection with these experiments. 

It was found in one or two instances that the nucleated pieces 
divided in the same way that the whole egg did, except that the blas- 
tomeres are proportionately smaller. From pieces of this kind whole 
embryos of small size developed. In this case we must suppose that 
the protoplasm has succeeded in rearranging itself into a new whole 
of smaller proportions.^ 

Crampton (*96) has shown in a moUusk, Ilyanassa obsoleta, that 
when a blastomere is separated from the rest, the cleavage proceeds 
as though the blastomere or its products were still present, and the 
larva is defective in those organs that are normally derived from that 
blastomere. These results are in line with those on the ctenophore 
^%Z' Fischel (1900) has also made some experiments on the seg- 
mented egg of the ctenophore, and has confirmed several of the results 
obtained by Driesch and Morgan. In addition he has tried the effect 
of disturbing the first-formed cells by pushing them over each other, 
so that their relative positions are changed. He finds as a result 
that the paddles, sense organ, etc., appear in unusual positions, and 
the latter may be doubled. This shows that we must regard the 
material or structural basis of the organs as present very early in 
the different parts of the egg, and that the organs develop without 
much regard to their relation to other organs. 

Ziegler (*98) has also made some observations on the egg of this 
same ctenophore, that bear directly on some of the questions here 
raised. His study of the cleavage shows that the micromeres arise 
from the part of the ^^^ that is opposite the pole at which the 
first cleavage furrow appears — the animal pole. Fischers results 
have shown that the paddles and the sense organs arise from these 
micromeres, for, if the latter are displaced the former are also. 

Ziegler performed the experiment of cutting off that part of an ^^% 
(which has just begun to divide) lying opposite the region in which 
the first furrow has appeared. In this way there was removed 
from the unsegmented egg the part from which the micromeres 

1 We offered as a possible explanation in this case that the egg had been cut in two 
symmetrically with reference to the eccentric nucleus. 



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REGENERATION IN EGG AND EMBRYO 24 1 

develop. Ziegler found that the micromeres still arise, and that from 
such pieces larvae develop that have eight rows of paddles and four 
endodermal sacs. In one case two of the sacs were smaller than the 
others ; in another case one of the four was very much smaller than the 
rest. In another operation a large piece was cut from the egg, leaving 
a small nucleated piece that divided into two blastomeres of unequal 
size. An embryo developed from this small piece with four endoder- 
mal sacs, and only four well-developed rows of paddles. The four 
rows of paddles that were lacking were represented by two groups of 
a few plates each. 

Ziegler gives a different interpretation of these results from that 
which Driesch and Morgan have offered. He interprets the last ex- 
periment, in which after the operation the piece divided into two 
unequal parts, and only four rows of paddles appeared, as meaning 
that the development of these organs on the smaller part is sup- 
pressed on account of the small size of the part. If the part had 
been still smaller all trace of the missing paddles might disappear, as 
he thinks was the case in certain experiments of Driesch and Morgan. 
There can be, I think, little doubt that if a piece is small enough, the 
result would follow as. Ziegler supposes. It does not seem probable, 
however, that the pieces were really below the lower limit in the 
experiments of Driesch and Morgan, since the smaller blastomere 
was in one case as large as the whole piece (/>. as both blastomeres 
taken together) in one of Ziegler's experiments. 

Ziegler's results show very clearly that we are not obliged to 
think of the substance of the micromeres as laid down in the proto- 
plasm of the egg, and hence there is no ground for supposing the 
substance of the paddles is necessarily present in the vegetative 
hemisphere of the egg. His results show that if the vegetative part 
is cut off, micromeres and paddles are still formed, although that 
part of the egg substance from which they normally arise has been 
removed. It should be pointed out, in this connection, that Driesch 
and Morgan did not suppose that the bases of the micromeres, or of 
the paddles, are actually laid down in a definite part of the proto- 
plasm of the egg. They had also observed that in some cases whole 
embryos arose after a part of the egg had been removed, and this 
they attributed to the symmetrical position of the cut in relation 
to the organization of the egg. Ziegler's operations were made more 
or less in this symmetrical plane, excepting the one that gave rise to 
an incomplete embryo. Driesch and Morgan held that the formative 
factors become localized in the protoplasm, rather than arise from 
the nucleus, but pointed out that these observations do not lead to 
His's conclusion of localized germ areas in the egg. 



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CHAPTER XII 

THEORIES OF DEVELOPMENT 

The experimental work that Pfliiger carried out in 1883 on the 
effect of gravity on the cleavage of the frog's egg, and the con- 
clusions that he drew from his experiments, mark the starting- 
point for the modern study of experimental embryology.* We can 
trace the influence of Pfliiger's results through most of the more 
recent work, and one of the conclusions reached by Pfliiger, namely, 
that the material of the egg may be divided by the cleavage planes 
in any way whatsoever without thereby altering the position of the 
embryo on the egg, is, I think, one of the most important results that 
has yet been reached in connection with the experimental work on 
the egg. Pfliiger's analysis of the factors that direct the develop- 
ment has also an important bearing on the interpretation of the 
development of a whole embryo from a part of an egg. 

Pfliiger found that in whatever position the frog's egg is turned 
before it begins to divide, the first two planes come in vertically, and 
the third horizontally, and that later the smallest cells are always 
formed in the upper hemisphere. He concluded, therefore, that 
gravity has some sort of influence in determining the position of the 
planes of cleavage. Pfliiger observed that the position of the median 
plane of the body of embryos that have developed from eggs turned 
into unusual positions does not, as a rule, correspond to the plane of 
the first cleavage, but that the embryo generally lies on that meridian 
of the egg that passes through the primary egg axis and the highest 
point of the egg in its new position. Since any meridian may happen 
to be placed uppermost, the embryo may, therefore, develop upon 
any one of the primary meridians, and hence the material must be 
isotropous around the primary axis. Furthermore, since the embryo 
appears always below the middle of the egg, in whatever position 
the egg may lie, we must conclude that in each meridian the material 
is also isotropic. 

It may be pointed out that while more recent work has substanti- 
ated, on the whole, the latter conclusions^ of Pfliiger, just stated, still 

1 These experiments have been quite fully described in my book on TAe Development of 
the Frog^s Egg. 

^ Not, however, the supposed action of gravity on the egg. 

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THEORIES OF DEVELOPMENT 243 

the results of studies of regenerative phenomena of organisms show 
that the conclusions are not necessarily the only ones deducible from 
the experiments; for, although it may be true that any possible primary 
meridian of the egg may become the median plane of the body of the 
embryo, it does not follow that there is no one organized plane always 
present in the normal egg, i.e, the egg may not be entirely isotropic. 
That this may be the case is shown in the regeneration of pieces 
of adult animals in which a piece cut to one side of the old median 
plane may develop a new plane of symmetry of its own. This possi- 
bility must be also admitted for the egg. If we substitute the term 
" totipotence,** meaning that any meridian of the egg has the possi- 
bility of becoming the median plane of the embryo, in place of 
Pfluger's term " isotropy,** we remove this element of possible error 
from his statement. 

Roux and Born have shown that the only action that gravity has 
on the frog's egg is to bring about a rearrangement of the contents 
of the egg, a phenomenon that Pfliiger had not observed. The lighter 
part flows to the highest region of the egg, and the heaviest to the 
bottom of the egg, hence the change in the. position of the cleavage 
planes observed by Pfliiger that begin in the upper, more protoplasmic 
part of the egg. 

Another series of experiments, that we also owe, in the first place, 
to Pfliiger ('84), consist in compressing the ^g% before and during 
its cleavage. The position of several of the cleavage planes may be 
altered, yet a normal embryo develops from the egg. The same 
experiment has been repeated by Hertwig ('93), and by Born (*93), 
on the frog's egg, and by Driesch C92), Ziegler ('94), myself ('93), 
and others, on the egg of the sea-urchin, with substantially the same 
results. The value of the experiment lies not so much in showing 
that the coincidence between the first cleavage planes and the orient- 
ing planes of the body may be lost, as in showing that under these 
circumstances the nuclei have a different distribution in the proto- 
plasm from that which they hold in the normal ^gg. Any theory of 
development that depends on the qualitative distribution of nuclear 
products during the cleavage period meets with great difficulties in 
the light of these results, and in order to overcome them will be 
obliged to add qualifications of such a kind as materially to alter 
its simplicity. Roux's theory, for instance, comes into this category. 
Roux ('83) suggested that since the complicated karyokinetic division 
of the nucleus is carried out in such a way as to insure a precise divi- 
sion of the chromatin, and since the qualities of the male are transmitted 
to the egg through the chromatin of the spermatozoon, it is probable 
that the division of the chromatin is a qualitative process, by means 
of which the elements are distributed to different parts of the egg. 

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244 REGENERATION 

According to Roux, the first division of the frog's egg divides the 
material of the right half of the embryo from that of the left ; the 
second division separates the material of the anterior half from that 
of the posterior half. Roux limited, to a certain extent, his hypothesis 
to these two divisions of the frog's egg, and stated further that it is 
not improbable that during the later stages of development there may 
take place an interaction of the parts on each other, and this inter- 
action would be another factor in the development. Weismann has 
adopted Roux's hypothesis, and has extended it to all organisms, and 
to most of the divisions of the developing egg, at least to all those 
divisions in which the qualities of the layers, tissues, organs, etc., are 
separated. On this slight basis he has constructed his theory of 
development and of regeneration It is important, therefore, to 
examine critically the evidence furnished by experimental embryology 
for or against this hypothesis of a qualitative division of the egg dur- 
ing the cleavage period. 

The development of a half embryo from one of the first two 
blastomeres of the frog's egg, in Roux's experiment, seemed to sup- 
port Roux's hypothesis, but it was not long before it was seen that 
the presence of the other blastomere vitiated the evidence to such 
an extent as to render it worthless, so far as this hypothesis is 
concerned. Then followed the experiments with the isolated blasto- 
meres of the sea-urchin, amphioxus, jelly-fish, teleost, ascidian, triton, 
etc., in which each blastomere, when completely separated, gives rise 
to a whole embryo. From these experiments Driesch and Hertwig 
drew the opposite conclusion, namely, that during the cleavage there 
is a quantitative division of the egg into blastomeres that are equiva- 
lent, or at least totipotent. Roux attempted to meet the results of 
these experiments in two ways. He pointed out that in several of 
these cases the isolated blastomere divides as a half or as a fourth 
of the egg, and that in the sea-urchin this leads to the formation of an 
open half-blastula. In the second place, Roux brought more to the 
front his subsidiary hypothesis of the reserve germ plasm. He sup>- 
posed that along with the early qualitative division of the nucleus, 
by means of which each part receives its particular chromatic sub- 
stance, there is also a quantitative division of a sort of reserve germ 
plasm contained in the nucleus. Each cell may receive also a part 
of this material, and hence each cell may contain the potentialities 
of the whole ^gg. This reserve plasm may be awakened by any 
change that alters the normal development, as, for instance, when 
the blastomeres are separated. It may take some time for this 
reserve stuff to wake up, as shown by the half-development of the 
sea-urchin's ^%g that goes on for some time after the separation 
of the blastomeres. This hypothesis cannot be objected to on purely 

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THEORIES OF DEVELOPMENT 245 

formal grounds, but we are not so much concerned with a purely 
logical hypothesis as with a verifiable one. 

It has been pointed out that the experiment of compressing the 
egg in different planes that leads to a new distribution of the nuclei 
is a formidable obstacle to Roux*s hypothesis. If the nuclear divi- 
sions in the compressed egg are of the same sort as in the normal 
egg, we should expect to find as a result either a monstrous form 
with all its parts misplaced, or, if the parts are mutually dependent, 
nothing at all. Roux has attempted to meet this case by supposing 
that the nucleus itself responds to the change in the protoplasm and 
alters its divisions in such a way as to send to each part of the com- 
pressed egg the right sort of material for that part. This means 
that the nucleus can so entirely change the sequence of its divisions 
that instead, for instance, of sending to each pole of the first spindle 
the material of the right and left sides of the body, as it does nor- 
mally, it may divide under compression in such a way that the 
material for the anterior half of the embryo is separated from that 
of the posterior half. That a change involving such a vast number 
of qualities could take place, as a result of the sUght compression on 
the egg that brings about a change in the position of the spindle, 
seems highly improbable. It is, of course, not a disproof of the 
hypothesis to show that it involves very great complications, for the 
very assumption itself of a qualitative division of the nucleus, in 
the Roux-Weismann sense, involves us in great complications. 

A more damaging criticism of the hypothesis of a qualitative 
division of the nucleus is found in an appeal to direct observation, 
which shows that the chromatin divides always into exactly equal parts. 
In many cases we know, from the subsequent fate of the cells, that 
two cells arising from the same cell play very different r61es in the 
subsequent development, yet the chromatin of the nucleus is always 
divided equally. 

The development of the isolated blastomeres of the ctenophore 
egg may seem at first sight to give support to Roux*s hypothesis, for 
in this case the first two cells are completely separated, and yet give 
rise to half-structures. Crampton's experiments on the eggs of 
ilyanassa may also appear to be evidence in favor of this view. 
In fact, however, they give no more support to the idea of a qualita- 
tive division of the nucleus than they do to that of a qualitative divi- 
sion in the protoplasm, and there are some further experiments on 
the ctenophore egg which indicate that it is the latter rather than the 
former sort of division that takes place. As stated in the preceding 
chapter, Driesch and Morgan found that, if a part of the protoplasm 
of the unsegmented egg of the ctenophore is removed, an incomplete 
embryo develops, although the whole of the segmentation nucleus is 

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246 REGENERATION 

present Ziegler's results show that, even after the removal of that 
part of the egg from which the micromeres develop, the segmenta- 
tion may still be like that of the whole egg, and this shows that the 
egg has great powers of recuperation (at least in a symmetrical 
plane), so far as its protoplasm is concerned. If, however, it is true 
that when a part is cut off unsymmetrically the protoplasm cannot 
reorganize itself, then the conclusion that Driesch and Morgan drew in 
regard to the protoplasm will hold, provided, as seems to be the case, 
the smaller blastomere of the first two is large enough to produce the 
typical structures. The main point is this : If the protoplasm re- 
adjusts itself after the operation, so that the piece divides as a whole, 
a complete embryo develops ; if, however, the protoplasm does not 
readjust itself, and the piece divides as a part, an incomplete em- 
bryo is formed. Since in both cases the same nucleus is present, 
and since the difference is obviously connected with a change in the 
1 protoplasm, it seems much more probable that the phenomenon of 
whole and half development is connected with the protoplasm and 
not with the nucleus. 

The hypothesis that Pfluger, Hertwig, and Driesch have adopted, 
namely, that the cleavage divides the egg into potentially equal parts, 
stands in sharp contrast to the Roux-Weismann conception of devel- 
opment. There are two ideas in the former view which should be 
kept, I think, clearly apart: the first is, that the blastomeres are 
potentially equal (isotropous), because they are exactly alike; the 
second is, that despite the differences that may exist amongst them 
they are still potentially able to do the same thing, i.e, they are toti- 
potent The former alternative is that adopted by Pfluger, Hertwig, 
and Driesch ; the latter view, to which Driesch seems more inclined 
in his later writings, is the one that I should prefer.^ The first 
four blastomeres of the sea-urchin's egg appear to be exactly alike, 
and we find that each can make a whole embryo. If we assume, 
however, that despite their likeness and their totipotence they are 
different in so far as there is present in the protoplasm a bDateral 
structure, we are nearer, in my opinion, to the truth ; for, unless we 
assume the bilateral structure to be determined later by some exter- 
nal factor, of which there is no evidence, we must suppose that after 
fertilization, at least, there must be a bilateral structure to the proto- 
plasm, and this view is borne out in one sense by the subsequent 
mode of cleavage of the blastomeres if they are separated. Whether 
this"" bilaterality of the fertilized ^^g leads to the bilaterality of the 
cleavage is, however, a different question. In some cases this 
appears to be the case, in others it is clearly not the case, and we 
must suppose that some other condition determines the bilaterality 

1 As stated in my article on " The Problem of Development,*V4^oa , 

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THEORIES OF DEVELOPMENT 247 

of the later stages than that which influences the cleavage. Many- 
facts of experimental embryology and of regeneration show, more- 
over, that a new bilateral structure may be readily assumed by 
pieces that have lost their connection with the rest of the organism. 

After the third division of the egg of the sea-urchin, four of the 
blastomeres are somewhat different, so far at least as the material of 
which they are made up is concerned, from the other four ; yet any 
one of the eight blastomeres, or groups of blastomeres, can produce 
a whole embryo. The same statement can be made for much later 
stages, since it has been found that fragments from any part of the 
blastula wall can give rise to whole embryos, and we may safely attrib- 
ute this property to all the cells, although on account of the size of the 
cells of later stages they cannot individually produce a whole embryo, 
but each can produce any part of an embryo, which amounts to the 
same thing. If we assume that all of these cells are exactly alike, 
as Hertwig has done, we fail to see how the next stage in the devel- 
opment could take place, unless some external factor could act in 
such a way as to change the different parts of the ^g%. We have, 
however, no reason to suppose that all the cells are alike because 
they are all potentially equal. Even pieces of an adult animal — of 
hydra or of stentor, for example — can produce new whole organisms, 
although we must suppose these pieces to be at first as unlike as are 
the parts of the body from which they arise. Moreover, we do not 
know of a single egg or embryo in which we cannot readily detect 
differences in different parts of the protoplasm. 

Can these gross differences, that we can see, in the materials of 
the egg explain the different development of the parts of the egg ? 
It can be shown, I think, that they do not necessarily determine the 
result. If we cut in two a blastula, so that one piece contains only 
the cells from the animal half and the other piece cells from the 
vegetative half, each produces a whole embryo; yet the one half 
lacked just those parts which by hypothesis were supposed to 
determine the gastrulation of the other half. If we suppose that 
the materials or structures that are characteristic of the vegetative 
half are gradually distributed from the vegetative to the animal pole 
in decreasing amounts, then any piece of the ^g^ will contain more 
of these things at one pole than at the other. If, then, it could be 
shown that the gastrulation depends on the relative amounts of these 
materials in the different parts of the blastula, the difficulty met with 
in the former view disappears in part. I say in part, because the rela- 
tive amount of materials that produces the results imj3lies a connect- 
ing substratum that is acted upon and determines the result. Even 
if we suppose that this polar distribution of material could account 
. for the polar invagination, we should still be at a loss to account for 

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248 REGENERATION 

the origin of the bilateral symmetry. In many eggs there is no evi- 
dence of a bilateral distribution of the material, although in some few 
cases there may be, so far as the form is concerned, a plane of bilat- 
eral symmetry. But even if it is supposed to be present in all eggs, 
and to coincide with the first plane of cleavage (or with any other 
cleavage plane), we still could not explain the bilateral symmetry of 
the one-half and one-fourth whole embryos that come from the corre- 
sponding isolated blastomeres. If a preexisting bilateral plane exists 
in the egg, it must be reestablished in some way in the isolated blasto- 
mere and in pieces of the blastula wall. In the latter case this could 
scarcely be brought about by a redistribution of the gross contents 
of the piece, since the presence of cell walls would interfere with such 
a process. 

This analysis shows, I think, that the transformation of a piece 
into a new whole really involves a change in the fundamental struc- 
ture itself. There cannot be much doubt that both the polarity and 
the bilaterality of the egg, or of a piece of the egg, belong fundament- 
ally to the same class of phenomena, and we are forced to the sup- 
position that they are inherent peculiarities of the living substance. 
Driesch thought at one time that it is only necessary to suppose that 
the protoplasm, and every part of it, possesses a primary polarity, 
and that some inequality in the material might determine the plane 
of bilaterality; but later he thought it necessary to assume also the 
presence of a bilateral structure in the protoplasm, and in all parts of 
it. This assumption of every part having a polar and a bilateral struc- 
ture, and the polarity and bilaterality of the whole being the sum 
total of those of all its parts, is, I think, insufficient to meet the situa- 
tion. If, for example, the first plane of cleavage coincides with the 
median plane of the body, the right blastomere has a structure that 
leads to the formation of the right side of the body, and similarly 
for the left blastomere. If the two blastomeres are separated, 
and each gives rise to a whole embryo with a new plane of bilateral 
symmetry, we must suppose that a new bilaterality has been 
produced. It does not make the problem any simpler to assume, as 
Driesch has done, that this is brought about by the elements re- 
arranging themselves bilaterally on each side of a new plane that 
passes through the middle of the isolated blastomere, for what we 
need to have explained is what determines the new median plane. 
It seems to me that the problem is not any simpler, if we assume the 
polarity and bilaterality to be the property of a large number of ele- 
ments, as Driesch has done, than if we assume at once the polarity 
and bilaterality as characteristic of the whole ^^'g. The difficulty of 
understanding how a new bilaterality can be induced in a piece of the 
whole is as great on the one assumption as on the other, Not only 

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THEORIES OF DEVELOPMENT 249 

is it, I think, a much simpler idea to suppose the structure is some- 
thing pertaining to the whole and is not the sum total of smaller 
wholes, but the idea is more in accord with other phenomena. 

We meet here, I think, with precisely the same problem that we 
meet with in the regeneration of parts of adult animals. If ia plana- 
rian is cut in two lengthwise, along the middle line, each half produces 
new tissue at the cut-side, out of which the missing half is formed. 
In this case the old median plane remains, more or less, as the median 
plane of the new worm, i.e. the structure of the new part is built 
up on that of the old. Very much the same result follows when the 
worm is cut longitudinally into two unequal parts. The larger piece 
retains its old plane of symmetry and adds to the cut-edge a new part 
that completes the symmetry. The smaller piece also builds up new 
material along the cut-edge, and a new plane of symmetry is formed 
between the old and the new parts. Here, also, a median plane 
is established at the edge of the old material, but in this case the 
material lay to one side of the old middle line, and this involves the 
changing over to a large extent of the old material, so that it fits 
in with the new structures of the new median plane. 

In those forms in which the readjustment takes place entirely in 
the old part, the change of conditions is more difficult to interpret. In 
some respects hydra gives us an intermediate condition, but since it 
is a radially symmetrical instead of bilaterally symmetrical form, the 
transformation is not so obvious. If a cylindrical piece is cut from 
the body, and is then cut lengthwise into two half-cylinders, each closes 
in and makes a cylinder of smaller diameter. A little new tissue 
may appear along the fused edges, but the missing half is not re- 
placed, and a new hydra with a body of half size is formed from the 
piece. It is to all appearances a radially symmetrical form, and we 
must think, in this case, of the new axis of symmetry as having shifted 
to the middle of the piece. As yet no similar experiments have been 
made on a bilateral animal that regenerates by morphallaxis, so that we 
have nothing to appeal to for comparison with the bilateral egg, but the 
results, just described for the planarian and for hydra, indicate how a 
change might take place in pieces of adult animals that would lead to 
the formation in them of a new symmetrical structure. If we imag- 
ine a case of this sort, and suppose that after separating a piece from 
the side the cut-edge closed in and the piece assumed a symmetrical 
form, it is conceivable that a new plane of bilateral symmetry might 
soon appear in the middle of the piece owing to the symmetrical form 
of the piece; or the new plane of symmetry might slowly shift from 
the cut-edge toward the middle of the piece, after reaching which the 
balance or equilibrium would be attained. This statement, it must be 
confessed, is little more than a supposition, and rests on the unproven 

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2 SO REGENERA TION 

assumption that the internal symmetry may develop in response to a 
symmetrical change in shape of the piece as a whole, which is partly 
the outcome of purely physical factors. At present, however, I see 
no other probable inference from the facts. 

If we suppose a bilateral structure is present in the fertilized egg, 
and that it corresponds to the first plane of cleavage, a change of the 
sort that we have just sketched above may be supposed to take place 
when the blastomeres are separated. The stimulus is found in the 
new spherical form assumed by the isolated blastomere, and we may 
imagine the change to take place, in the way indicated, by virtue 
of the old bilaterality that is present, the change beginning at the 
side originally in contact with the other half. 

There are several facts which seem to indicate that a change in the 
axial relations of the egg is very easily brought about before any 
definite organs have appeared. The fact that the point of entrance 
of the spermatozoon in the egg of the frog ^ and of the sea-urchin ^ 
may determine the first plane of cleavage points to this conclusion. 
The fact that, in the frog, and also in the triton, the median plane of 
the embryo corresponds sometimes to the first, sometimes to the 
second plane of cleavage, and sometimes to neither one, shows that 
the bilaterality of the embryo-structure may or may not coincide with 
the plane of cleavage. In the fish also there seems to be no corre- 
spondence between the planes of cleavage and those of the embryo, 
so that different factors may determine the two. We should not be 
justified in concluding from this evidence that a bilateral structure is 
absent, but rather that it is of such a sort as to be independent of 
r the cleavage, and that it can be also easily changed. It is prob- 
able that the kind of organization that we must suppose to exist in the 
egg is of a very simple sort, and capable of easy readjustment. There 
is certainly no evidence in favor of the view that the organization of 
the egg need be anything like the organization of the embryo that 
comes from the tgg, although the organization of the ^%^ may be 
perfectly definite in its character. Until we know more of the nature 
of this organization, it is useless to speculate further as to how it can 
be altered. 

Another question of much importance in connection with our 
present topic is the part played by the individual, cells in the 
early development of the whole ^g^, or of any part of the egg. 
Hertwig ('93) thinks that the development is brought about by the 
action of the individual cells on each other. Driesch, when he states 
thiit the fate of a blastomere is a function of its position in the whole, 
docs not commit himself definitely one way or the other so far as the 
cell as a unit is concerned. Whitman and others have urged the 

^ According to Roux. ^ According to E. B. Wilson. 

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THEORIES OF DEVELOPMEiVT 2$! 

insufficiency of the cell theory, and think that cell boundaries play 
no important part in the development, but that the embryo develops 
as a whole. This has seemed to me to be the more probable view in 
the light of certain results of experimental embryology. Driesch, in 
later papers, has also opposed Hertwig's idea, and Wilson in his book 
on TAe Cell has also, to a certain extent, adopted this point of 
view. The formation of a typical larva in the sea-urchin and in am- 
phioxus out of one-half or one-fourth the whole number of cells 
demonstrates, I think, the insufficiency of the cell-unit hypothesis. 
The discovery of continuous protoplasmic connections between neigh- 
boring cells, and the formation of new protoplasmic connections 
between all regions, as found by Mrs. G. F. Andrews,^ gives us a 
basis of fact on which to rest the hypothesis of the embryo being a 
whole structure. This view meets with no great difficulty on the 
grounds that the nuclei are distinct centres of metabolic activity, for 
we know at present so little of what sortof action takes place between 
the nucleus and the protoplasm that we cannot rest our argument on 
any demonstrable relation. 

The discovery that pieces below a certain minimum size are inca- 
pable of producing a whole organism is of capital importance. It 
has been pointed out that pieces of the egg of the sea-urchin less than 
one-sixteenth of the whole do not produce even the gastrula stage. 
In amphioxus the one-eighth blastomere seems to be near the lower 
limit of development. It has also been found that there is a lower 
limit for pieces of adult organisms below which they do not regen- 
erate. This has been shown for hydra, tubularia, planarians, and 
stentor, and is probably true for all forms. This result is especially 
interesting in those cases in which the parts contain all the elements 
necessary to produce a new organism, and come from parts of the body 
that are totipotent in these respects. It seems certain that the 
lack of power of development in these cases is due entirely to the 
smallness of the piece. We can express the idea in another way by 
stating that a certain volume is necessary in order that a piece may 
produce the typical organization. This conclusion is important as 
showing that the organization is something enormously large as com- 
pared with the size of the chemical or physical molecules, and even 
of the crystal molecule. The size of a piece that is at the lower 
limit of organization is also very much larger than the smallest cells 
of which the embryo is made up, and this relation is a point in favor 
of the view that the organization is not simply the resultant of the 
interaction of the cells, but is something much larger than these cells ; 
and we may even go further, I think, and add that it dominates the 
cells rather than is controlled by them. 

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252 REGENERA TION 

In the light of the questions discussed in the preceding pages, we 
may now attempt to follow out in a more connected way some of the 
modern views and hypotheses dealing with the problem of develop- 
ment. 

Hertwig, as we have seen, has opposed the Roux-Weismann 
hypothesis, and has formulated a view of his own. According to 
Hertwig, the cleavage divides the egg into equivalent parts, — an idea 
very similar to that of Pfluger. The cells he regards as units, and 
the development as the result of the interaction of the cells, — a 
process that in a way Roux had also assumed to take place between 
the different parts of the later- embryo; Thus, while Hertwig's hy- 
pothesis contains little that is really new, it has selected portions from 
several already existing hypotheses, and united them into a consistent 
whole. It has been objected to Hertwig's view that the interaction 
of equivalent cells could never account for the introduction of new 
processes in the development; but if we grant that the cells are 
never entirely equivalent, whatever their potence may be, this objection 
can, I think, be met. Hertwig*s chief service has been his destructive 
criticism of the Roux-Weismann idea of qualitative nuclear division. 

Hertwig maintains that each stage in the development is the cause 
of the next stage, and states that a description of the series of stages 
through which the embryo passes gives a causal knowledge of the 
phenomena of development. He claims that beyond this descriptive 
knowledge we cannot hope to penetrate. Both Roux and Driesch 
have taken issue with Hertwig, and have pointed out that while each 
stage in the development contains within itself the causes of the suc- 
ceeding stage, yet we gain no idea as to these causes from a simple 
description of two consecutive stages themselves. To state that the 
fertilized egg is the cause of the cleavage gives us no idea of what 
sort of a process the cleavage is, or how it arises, or what determines 
the sequence of the divisions, etc. The blastula, for instance, con- 
tains the factors that produce the gastrula; but to state that, in a 
physical sense, the blastula is the cause of the gastrula is an erroneous 
interpretation of what is meant by causal knowledge. If Hertwig's 
idea were correct, there would be as many causes in each embryo as 
there are stages in its development, and as many causes in the whole 
range of embryology as there are forms that develop multiplied by the 
number of stages in each embryo. What we should seek to discover 
is the particular cause that brings about each kind of process. If 
we could discover the cause in one single case, it is highly probable 
that it would be found to extend to a large number of other cases. 

Driesch formulated an hypothesis of development in his Ana- 
lytische Theorie^ but has modified and changed it in several later 
contributions. It is difficult to give in a few words the subtile analysis 

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THEORIES OF DEVELOPMENT 253 

which Driesch has made of the phenomena of development. His ana- 
lytical theory rests on the dictum that the prospective value of each 
blastomere is a function of its position in the whole. By ** function " is 
meant " a relation of dependence of a general unknown kind." This 
idea is connected with the following one, viz. that any blastomere 
could be interchanged with any other one without altering the end- 
result A few elementary processes are supposed to be "given " in 
the structure, or in the composition of the egg. Each elementary 
process is the outcome of a cause, and each elementary process must 
release the succeeding causes, — i.e, if the organization of the phase 
A is present, one of the causes of the next phase B is also then present. 
The first elementary process is the cleavage, that is initiated ("aus- 
gelost") by the fertilization. After a fixed number of divisions has 
taken place, the cleavage process comes to an end. It has led to the 
production of a number of cells having similar nuclei but having a 
different plasma structure, and the result is the blastula stage. Or- 
gans whose formation starts from the blastula stage arc called primary 
organs ; the archenteron, the mesenchyme, the ciliated band, and the 
mouth of the sea-urchin embryo belong to this class. Secondary 
organs are those that arise from the primary ones, as the coelom sacs, 
for instance, in the ^ sea-urchin embryo. The primary organs are 
started by the setting free("Auslosung**) of a new elementary process 
in the blastula, and later the secondary organs are started by new ele- 
mentary processes that arise in the gastrula, which cannot appear until 
the gastrula stage itself is present as a starting-point. In other 
words, the elementary processes that are "given" in the egg can 
only come into action, or be set free after a certain stage has come 
into existence. This means that we must think of each organ that 
responds to a stimulus as having the possibility of receiving that stimu- 
lus, and also of answering to it. Even in inorganic nature every reac- 
tion must depend on a specific receptiveness and a specific answer. 
Driesch supposes that the receptivity is in the protoplasm, and the 
power to respond is in the nucleus of each cell. In this way he 
attempts to meet the difficulty that the nucleus is, in every cell, the 
bearer of the totality of all the " Anlagen" ; but inasmuch as it is sur- 
rounded by a specific plasma, it is in a position to receive only cer- 
tain stimuli, and can therefore only respond to certain causes. 

In the specific nature of the cytoplasm of the cell lies the pro- 
spective potence of every organ, and the possibilities of each cell are 
limited by its plasma ; th^ cell becomes more and more limited as 
development proceeds. It may be said, therefore, that in the course 
of development the cells become actually limited in their possibilities, 
although they may still retain within themselves, in the nucleus, the 
potentialities of the entire organism. 

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254 REGENERATION 

In the course of development each causal reaction brings about 
not only chemically specific differences, and thereby makes possible the 
introduction of new elementary processes, but the reaction also brings 
about by this very means a lessening of the possibilities of the cell, 
because each cell will now only respond to a more limited set of 
causes. We may say that the elementary process is not only the 
cause of the next change, but by virtue of its specific nature it is the 
beginning stage of the future reactions. Development proceeds from 
a few prearranged conditions, that are given in the structure of the 
Q^'g^ and these conditions, by reacting on each other, produce new 
conditions, and these may in turn react on the first ones, etc. With 
every effect there is at the same time a new cause, and the possibility 
of a new specific action, i.e, the development of a specific receiving 
station for stimuli. In this way there develops from the simple con- 
ditions existing in the egg the complicated form of the embryo. 

In this brief summary of some of the essential features of Driesch's 
hypothesis, I have omitted some parts that seem to me to go beyond 
the legitimate field of a scientific hypothesis, — such, for instance, as the 
causal harmony of the reactions ; and other parts have been omitted 
because they are improbable in the light of more recent work. It 
would not be difficult to show that many difficulties beset each stage 
of the argument, or to show how slender a basis of fact there is to . 
support some of the hypotheses. In fact, Driesch himself has modi- 
fied very greatly some of the views of his Analytische Theorie in his 
later writings. The merits of the analysis should not be overlooked, 
however, since it is one of the first philosophical attempts to show how, 
in the light of recent discoveries, the process of epigenetic develop- 
ment may receive a causal interpretation. Even if the argument 
should break down, the hypothesis will remain an interesting contribu- 
tion, opening the way to newer points of view in regard to the process 
of development. In later papers, especially in those dealing with the 
localization of morphogenetic processes, Driesch attempts to show that 
certain experimental results demonstrate that there is a vitalistic prin- 
ciple at work in the development of the organism from the egg, as 
well as in the process of regeneration. He bases his argument on the 
results of the experiment in which the gastrula of the sea-urchin egg 
is cut in two, as described already on page 234. The archenteron has 
not, at the time of the experiment, subdivided itself into its three char- 
acteristic parts. The posterior piece, that contains the posterior part 
of the archenteron (the anterior part having been removed with the 
anterior piece), produces a new whole embryo of smaller size, in which 
the archenteron is subdivided into three parts, that are in the same 
proportion to each other and to the whole embryo as are the same 
divisions of the normal archenteron. This proportionate formation of 

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THEORIES OF DEVELOPMENT 255 

the parts of the archenteron on a smaller scale cannot, Driesch claims, 
be accounted for on any known chemical or physical principle. 
There. must be, therefore, a different sort of principle involved, and 
this Driesch calls the vitalistic principle. 

It may be pointed out that this illustration that Driesch has se- 
lected is only an example of all proportionate development, which 
many observers have described as taking place in pieces of em- 
bryos. It is only a striking case of what has been also known in 
many cases of regeneration, of small pieces producing whole struc- 
tures, and there is nothing new or startling in this demonstration of 
a vitalistic principle. The fact may be stated in another way, viz. 
that the proportionate development of an organ is, within certain 
limits, self-determining, or is self-determined by its size. The vital- 
istic principle that Driesch sees demonstrated in these results is 
the now familiar process of a smaller piece producing the typical 
structure on a smaller scale ; a phenomenon that a number of other 
writers had already called attention to as one of the most remark- 
able phenomena connected with the regeneration of pieces of an adult 
organism, or of an egg. 

It is something of this same sort that the older zoologists must 
have had in mind when they spoke of " formative forces " as peculiar 
to living things. The use of the word "force" in this connection has 
often been objected to, and not without justification ; since it seems to 
imply that the action is of the sort for which the physicist uses the 
word "force." The fundamental question turns upon whether the 
development of a specific form is the outcome . of one or more 
"forces," or whether it is a phenomenon belonging to an entirely 
different category from anything known to the chemist and the 
physicist. If we state that it is the property of each kind of living 
substance to assume under certain conditions a more or less constant 
specific form, we only restate the result without referring the process 
to any better-known group of phenomena. If we attempt to go 
beyond this, and speculate as to the principles involved, we have 
very little to guide us. We can, however, state with some assurance 
that at present we cannot see how any known principles of chemistry 
or of physics can explain the development of a definite form by the 
organism or by a piece of the organism. Indeed, we may even go 
farther and claim that it appears to be a phenomenon entirely beyond 
the scope of legitimate explanation, just as are many physical and 
chemical phenomena themselves, even those of the simplest sort. 
To call this a vitalistic principle is, I think, misleading. We can do 
nothing more than claim to have discovered something that is present 
in living things which we cannot explain and perhaps cannot even 
hope to explain by known physical laws. 

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2 56 REGENERA TION 

Wilson ('94) has also rejected Roux's hypothesis of qualitative 
nuclear division, and adopts the view of the totipotence of the early 
blastomeres. He has also advanced the view that there is during 
development a progressive differentiation of the cells. In a later con- 
tribution ('96), he accepts " the view of Hertwig and of Driesch that 
the various degrees of partial development beginning with the echino- 
derm egg and culminating in the gasteropod may be due to varying 
conditions of the egg cytoplasm in the different forms." Wilson 
points out that the series of forms represented at one end by amphi- 
oxus and at the other end by the ctenophore and the gasteropod may 
be brought under a common point of view, " for it is certain that 
development must be fundamentally of the same nature throughout 
the series, and the differences must be of secondary moment" 

If we reject, as several students of experimental embryology and 
of regeneration have done, the Roux-Weismann idea of the existence 
of pre-formed germs in the nucleus, and also the idea of Hertwig of 
the equivalency of the first-formed blastomeres, and Driesch's vitalis- 
tic principle, what position can we take in regard to the problem of 
development.? We may at least attempt to formulate our present 
position. 

There must be assumed to exist in the egg an organization of 
such a kind that it can be divided and subdivided during the cleavage 
without thereby losing its primary character. The refusion of the 
cells after each division by means of protoplasmic connections indi- 
cates how this may be possible. The organization must be thought 
to be of such a kind that the factors determining the cleavage may 
be different from those that determine the median plane of the body. 
This is demonstrated by Pfliiger's experiment in which the position of 
the cleavage planes is changed, but the embryo appears in relation to 
the primary meridians. The first-formed blastomeres, that result 
from the division of the egg, do not seem to be strictly equivalent, 
but they appear to be in most cases, at least, totipotent. The char- 
acteristics of each part of the protoplasm may be a factor in determin- 
ing what sort of structure may come from that part of the egg, but 
back of this lies the fundamental character of the protoplasm itself, 
that determines what each part, in its relation to the whole, can do. 
The division of the nucleus appears to be in all cases an exact quan- 
titative division, and there is some evidence to show that the early 
nuclei are all equivalent, — or at least totipotent. The division of the 
protoplasm is often into unlike parts, and the kind of cytoplasm con- 
tained in a part may or may not limit the potencies of each part 

One of the most important facts in connection with the organiza- 
tion is that a part, if separated from the rest, may become a new 
whole, and this appears to be a fundamental peculiarity of living 

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THEORIES OF DEVELOPMENT 2$? 

things. Analogies can be found, perhaps, in inorganic phenomena, 
as for instance a storm dividing into two or more parts and each 
developing a new storm centre of its own, or when a suspended drop 
is divided and each half becomes a new sphere ; but these comparisons 
lack some of the essential features of the organic phenomenon. 

A progressive change takes place as development proceeds, so that 
a stage once passed through is not repeated if a part is separated from 
the rest, as illustrated by Driesch*s experiments with the blastula and 
gastrula of the sea-urchin and starfish, and by the method of develop- 
ment of pieces of the adult, that do not pass through the embryonic 
stages. As the protoplasm changes new conditions may arise, either 
because the protoplasm in its new form can be acted upon by those 
internal or external conditions to which it did not respond at first, as 
Driesch has supposed, or, as I think equally probable, because the 
series of reactions that have begun with the first step in the develop- 
ment work themselves out in the same way that a chemical reaction 
once started may pass through a long series of stages depending upon 
the nature of the substance. The difference between these views lies 
in this, that the former supposes latent substances, or elementary 
processes or forces, whatever they may be called, to be present in the 
egg and to act when a medium that responds to them has come into 
existence; the other idea supposes that the whole process is started with 
the first change and once set going is of such a kind as to continue 
to an end through a regular series of stages. Both views are suppo- 
sitions, and, it may be, reduce themselves ultimately to the same thing. 

On any theory of development, the nucleus cannot be left out of 
account, since the evidence that we now possess shows that through 
the nucleus even the most trivial peculiarity of one parent, and prob- 
ably of both, may be transmitted. This has led a number of zoolo- 
gists to look upon the nucleus as a body containing specific elements 
corresponding to those of the individual from which the nucleus has 
come, but inheritance through the nucleus is no more a demonstration 
of the existence of pre-formed elements of the male than are the gen- 
eral facts of embryology a demonstration of pre-formation. All we can 
legitimately conclude is that the substance of the nucleus is of such a 
sort that it acts on the cytoplasm in a definite way, and determines, 
in part at least, its differentiation. There has been steadily accumu- 
lating evidence to show that during development there is an inter- 
change of material between the nucleus and the protoplasm, and it is 
not going far afield to conclude that the character of both nucleus 
and protoplasm is altered by the interchange in material. If this is 
admitted it is no more remarkable that a hybrid is midway between 
its parents than that a parthenogenetic egg produces a form like that 
of the individual from which it has come. 

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258 REG EN ERA TION 

Several writers, as we have seen, have adopted the view that the 
nuclei are storehouses of the undifferentiated germ plasm, and retain 
everywhere the sum total of the " Anlagen" of the egg nucleus. I do 
not know of any evidence that demonstrates that the nucleus is less 
modified in these regards than is the rest of the cell. On the con- 
trary it seems to me that a fair case might be established in favor of 
the view that the nucleus and the cytoplasm cannot be contrasted in 
this way, and that a change in the cytoplasm may also involve a 
change in the nucleus. 

The phenomena of regeneration show over and over again that 
differentiated cells may change into structures entirely different from 
what they have been, as illustrated in the development of the lens 
from the edge of the iris, and in the production of a new hydra, or 
tubularian, from a piece of an old one. It is, I think, an arbitrary 
assumption to suppose that this is brought about by a reserve stuff in 
the nucleus, for the production of new eggs and spermatozoa in the 
animal, from cells that have themselves passed through most of the 
early embryonic changes and have been parts of embryonic organs, 
shows that although the protoplasm may change throughout these 
stages, it may still come back to the starting-point, and there is 
nothing to show that this return is brought about by the nucleus. I 
cannot but think that Driesch was prejudiced by current opinion, 
when he adopted the view, as one of the foundations of his analytical 
theory, that the nucleus contains all the " Anlagen " of the whole or- 
ganism, and that the protoplasm alone undergoes a progressive change. 

The central problem for embryology is the determination of what 
is the cause or causes of differentiation. Our analysis leads us to 
answer that it is the outcome of the organization; but what is the 
organization ? This it must be admitted is a question that we cannot 
answer. Looked at in this way the problem of development seems 
an insoluble riddle ; but this may be because we have asked a ques- 
tion that we have no right to expect to be answered. If the physicist 
were asked what is gravity he could give no answer, but nevertheless 
one of the greatest discoveries of physics is the law of gravitation. 
If we could answer the question of what the organization is to which 
we attribute the fundamental phenomenon of development, there 
would perhaps be nothing further left to find out in the development 
of animals. Fortunately there is a different and safer point of view. 
There are other questions to which we can expect an answer. Be- 
cause the physicist cannot tell what gravity is, he neither rejects the 
term nor despairs of obtaining a knowledge of how it acts. If our 
analysis of the problem of development leads us to the idea of an 
organization existing in the egg, our next problem is to discover how 
it acts during development. Most of the results described in several 

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THEORIES OF DEVELOPMENT 259 

of the preceding chapters have taught us something of how the 
organization behaves. We have found that it can be affected by 
external circumstances, even to such an extent that its polarity may 
be reversed. We have seen that if an organized structure is broken 
up into pieces, each piece may reorganize itself into a new 
whole. The most familiar, and at the same time the most difficult 
thing to understand, is that the organization is of such a kind that it 
has the property of passing through a definite series of stages leading 
to a typical result, and having reached its goal of throwing off organ- 
ized bodies, or germ cells, that begin once more at the starting-point 
and pass through the same cycle. The action of the organism is 
sometimes compared to that of a machine, but we do not know of any 
machine that has the property of reproducing itself by means of 
parts thrown off from itself. 

These are some of the most characteristic phenomena exhibited 
by the organization. In the final chapter some of the questions that 
have been suggested in connection with the method of action of the 
organization will be further discussed. 



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CHAPTER XIII 
THEORIES OF REGENERATION 

It is significant to find that the theory of pre-formation of the 
embryo in the egg, that was so very widely held during the seventeenth 
and eighteenth centuries, and during the first part of the nineteenth 
century, was at once applied to the explanation of the regeneration of 
animals when this process became known. Bonnet in 1745 attempted 
to explain the newly discovered facts in regard to the regeneration of 
animals by means of the pre-formation theory. Just as the egg was 
supposed to enclose a pre-f ormed germ, so he imagined there lay con- 
cealed latent germs in the adult animal. At first Bonnet thought that 
these germs must be whole germs, like those contained in the germ 
cells of the reproductive organs, and that only as much of any one 
developed as was needed to replace the missing part. Later, how- 
ever, he admitted that the germs might be incomplete germs, which 
are so located in each region that they represent the parts of the 
body beyond that region. The purpose of these germs is to replace 
any accidental injuries to the animal. He pointed out that some 
animals are more subject to injuries than others, and these animals 
are he thought especially well supplied with germs. Since in some 
animals the same part may be replaced several times, Bonnet assumed 
that on each occasion a new germ is awakened. As many sets of 
germs are present in these animals as the number of times the animal 
is liable to be injured in the course of its natural life. 

Bonnet found that in lumbriculus a new head and a new tail may 
appear at almost any level, if the worm is cut in two, and, therefore, 
he supposed, head germs and tail germs are present throughout the 
worm. But why, if this is so, should a head germ always develop at 
the anterior end, and a tail germ at the posterior end of a piece cut 
from the body .^ Bonnet's keen mind saw that it was necessary to make 
a further assumption. He supposed that the fluids of the body that 
pass forward carry nourishing substances for the head. When the 
worm is cut in two these substances are stopped at the anterior cut- 
surface, and there accumulating act on the latent head germ, and 
nourishing it, cause it to develop. Correspondingly the nourishing 

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THEORIES OF REGENERATION 26l 

substances for the tail flow backward, and accumulating at the pos- 
terior cut-surface awaken a tail germ to activity. 

The part of the body in which these nourishing substances are 
supposed to be produced is not specifically stated, but in one passage 
Bonnet says that the fluids that flow toward the head are there 
used up in that organ, and we may infer that he held a similar view 
for the posterior region. He offers no explanation of the cause of 
the flow of these substances in a given direction, and in this respect 
his hypothesis lacks support where it is most needed. In fact, it is 
no more improbable that a head germ should always develop at the 
anterior end and a tail germ at the posterior end, than that head- 
forming substances should flow in one direction and tail-forming in 
another. It is not that it is worth while to object to Bonnet's hypothe- 
sis on the ground that it does not explain everything, but it is worth 
while to point out that it gives only the appearance of an explanation, 
and that it begs the whole question by the assumption of particular 
nourishing fluids flowing in definite directions. So far as the blood 
is concerned, we know that the different parts of the body take from 
it those substances or fluids that they make use of, not that special 
fluids flow to particular regions. It is probable that Bonnet thought 
of the blood rather than of any other subtler fluids passing through 
the tissues ; and, if so, there is nothing that we know in regard to the 
behavior of the blood that lends support to Bonnet*s idea. 

Bonnet takes care to state that the pre-formed germs may not 
appear to us like miniature copies of the part into which they develop, 
but they are so constructed that, as they absorb nourishment and 
become larger, they assume a characteristic form. 

Weismann, who has also accepted the pre-formation hypothesis to 
account for the development of the egg, has applied the same concep- 
tion of pre-formation to the process of regeneration. He believes that 
partial, latent germs are present in different parts of the body, and 
that these germs are present especially in animals that are liable to 
injury and in those parts of the body that are likely to meet with 
accidents. In these essential respects, Weismann's idea is the same 
as Bonnet's; but in regard to the location of the germs, and their man- 
ner of awakening, and as to how the forms, liable to injury, have ac- 
quired their power to regenerate, Weismann adopts more modern 
standards. He believes that the germs are located in the nucleus. 
Those that bring about the development of the ^gg are supposed to 
be different from those that bring about regeneration, because the 
method of regeneration is generally different from the method of 
development of the egg. 

Regeneration, on Weismann's view, is brought about by latent 
cells containing pre-formed germs in the chromosomes of the nucleui^ 



262 REGENERATION 

These germs are called the determinants. Since at each level in an 
animal, or in a part of an animal, regeneration may occur and re- 
place the missing part, it is assumed that the germs are correspond- 
ingly different at each level, and represent all the parts that lie 
distal to that region. Weismann does not suppose that there is a 
single germ at each level that represents all the distal parts, but that 
in each layer, or organ, or part there are many cells that contain 
germs corresponding to the distal regions. The qualities of the 
latent cells are sorted out by means of the qualitative divisions of the 
chromatic material of the nucleus. Moreover, since the new part can 
itself regenerate, the further assumption is made that during regen- 
eration new subsidiary or latent cells are laid down at each level. 
This is supposed to be brought about by a quantitative division of 
each germ after it has reached its definitive position in the new part. 

Weismann's general attitude toward the problem of regeneration 
is summed up in the following statements : " It may, I believe, be 
deduced with certainty from those phenomena of regeneration with 
which we are acquainted, that the capacity for regeneration is not a 
primary quality of the organism, but that it is a phenomenon of adap- 
tation'* Again, " Hence there is no such thing as a general power 
of regeneration ; in each kind of animal this power is graduated ac- 
cording to the need of regeneration in the part under consideration." 
" We are, therefore, led to infer that the general capacity of all parts 
for regeneration may have been acquired by selection in the lower 
and simpler forms, and that it has slowly decreased in the course of 
phylogeny in correspondence with the increase in complexity of 
organization, but that it may, on the other hand, be increased by 
special selective processes in each stage of its degeneration in the 
case of certain parts which are physiologically important and at the 
same time frequently exposed to loss." 

The evidence brought forward in the preceding pages leads, I 
think, to precisely the opposite conclusions, and, in certain cases at 
least, it has been shown that there can be no relation between the 
power of regeneration and the extent of exposure of a part to injury 
or to loss. It is unnecessary to enter here further into this question, 
since it has been discussed already in Chapter V. 

Weismann's statement that the power of regeneration has de- 
creased *' in correspondence with the increase in the complexity of the 
part " cannot by any means be entirely accepted. If the complexity 
of a part is of such a kind that the part cannot sustain itself indepen- 
dently until regeneration has taken place, or if the exposed surface of 
the wound is such that it cannot be closed over, or if the new part 
cannot be properly nourished, or if the tissues have changed in such 
a way that their cells can no longer multiply, then the statement is, to 

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THEORIES OF REGENERATION 263 

a certain extent, true. On the other hand, when we find that one of 
the most complicated organs of the body, the eye, can regenerate in 
the salamander, if only a piece of the optic cup is left attached to the 
nerve, we may well doubt if there is any such direct and general con- 
nection between regeneration and complexity as Weismann maintains. 

Weismann's so-called " mechanism '* of qualitative nuclear division 
is the basis of his conception of pre-formation. We are, I think, at 
present in a position to reject not only this conception, since it finds 
no support either in observation or experiment, but also his view that 
regeneration is brought about by latent cells ; for it has been shown 
in a large number of cases that the new cells come directly from the 
old, differentiated ones. In a previous chapter it has been pointed 
out that Weismann's idea that regeneration has been acquired by a 
process of natural selection, and is under the influence of this sup- 
posed agent, is in direct contradiction to a number of known facts. 
Under these circumstances we are warranted, I think, in concluding 
that the entire Weismannian point of view is wrong. 

The process of regeneration has been often compared to the pro- 
cess by which a broken crystal completes itself. Herbert Spencer, in 
particular, has elaborated this idea. In his book on the Principles of 
Biology, he says : ** What must we say of the ability an organism has 
to recomplete itself when one of its parts is cut off } Is it of the same 
order as the ability of an injured crystal to recomplete itself.? In 
either case new matter is so deposited as to restore the original out- 
line. And if, in the case of a crystal, we say that the whole aggregate 
exerts over its parts a force which constrains the newly integrated mole- 
cules to take a certain definite form, we seem obliged, in the case of 
the organism, to assume an analogous force." Spencer has called 
attention to a superficial resemblance between the renewal of a part 
of a crystal and the regeneration of an animal, and without further 
inquiry into the profound differences between the processes, assumes 
that "analogous forces" are at work. Now that we know something 
more of both processes, we find so much that is totally different, that 
there remains no basis for Spencer's conclusion, namely, that analo- 
gous forces must be present. Furthermore, Spencer's statement that 
the whole crystal aggregate exerts over its parts a force of some kind 
is diametrically opposed to our idea as to the method of "growth " of 
a crystal in a saturated solution. The new material is added always 
at the surface of the crystal, and the growth of each point is self-de- 
termining. There is no central force that controls the deposition of 
new material in the different regions. Rauber's work on the so-called 
regeneration of the crystal has given us a clearer conception of how 
the process is brought about. He has shown that when a piece is 
broken from a crystal, and the crystal suspended in a saturated solu- 

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264 REGENERATION 

tion of the same substance, it becomes larger by the deposition of 
new material oi^er all its surfaces. The addition of new material may 
be more rapid over the cut-surface than elsewhere, but it must not be 
supposed that the more rapid " growth " takes place in order to com- 
plete the form of the crystal, for the growth over the cut-surface fol- 
lows precisely the same laws that regulate the "growth " over all the 
other surfaces, that is taking place at the same time. In this respect 
we find an essential difference between the regeneration of a crystal 
and that of an animal, since in the latter the growth takes place only 
over the cut-surface ; and, in forms that regenerate by proliferation, at 
the expense of the old material, so that the old material is correspond- 
ingly diminished as the new part grows larger. Regeneration may 
even take place in an animal deprived of all food, and also in one that 
is starving to death and diminishing in size. In those forms that re- 
generate by a change in shape of the entire piece into that character- 
istic of the typical form, the process bears not even the remotest 
resemblance to the process in the crystal. It is so obvious from 
every point of view that the comparison is entirely a superficial one, 
that it seems useless to point out further differences between the two 
processes. 

Pfliiger ('83) has given, in brief outline, an hypothesis to account 
for the process of regeneration. He states that since there is always 
replaced exactly what is lost, the new part cannot arise from a pre- 
existing whole germ. If, for instance, the leg of a salamander is cut 
off at any level, as much comes back as is removed. The assumption 
of a leg germ is insufficient to account for the fact that only as much 
comes back as is lost, and not always a whole leg. Pfliiger, there- 
fore, offers another hypothesis. He assumes that food material is 
taken up at the wounded surface and organized into the substance of 
the new part. The new material is laid down at the surface of the 
old material, and is then organized into the kind of tissue that lay 
just beyond that region in the whole limb. Upon this first layer a 
new layer is deposited that is organized into the next part of the limb, 
and so on, until the whole missing part is replaced. Pfliiger does 
not give any idea of how the new material is deposited at the cut-sur- 
face, but from what we know of the histology of the process we must 
suppose, if we should adopt Pfluger's interpretation, that new cells 
are produced by the old ones,*and that these new cells form the suc- 
cessive layers out of which the new limb is produced. Pfliiger speaks 
of an arranging molecular force, which we can only suppose, in the 
light of what has just been said, to act from cell to cell through the 
continuous protoplasm. Pflijger also pointed out that in certain cases 
the organization can take place only in a certain direction, that is, in 
some forms regeneration can take place from one side of a cut-sur- 



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THEORIES OF REGENERATION 265 

face, but not from the other. He interprets this as due to a polariza- 
tion of the protoplasm, one surface having peculiarities that are 
absent in the other. 

There are certain objections to Pfluger's hypothesis that suggest 
themselves. In the first place the new part does not, in many cases, 
replace all that has been removed, and hence it is diflficult to see 
how the building up in the way Pfluger supposes, could take place. 
In these cases the new material forms only the distal end of the 
part removed, and the relation of the old to the new part is of sec- 
ondary importance. Again, in cases of heteromorphosis, as when a 
tail develops on an anterior cut-surface of a piece of an earthworm, 
the result must be due to quite different factors from those suggested 
by Pfluger. The results are, in fact, the reverse of what the hypoth- 
esis demands. Furthermore, when the entire piece is transformed 
into a whole new organism, there is very little in the process to sug- 
gest a change like that postulated by Pfluger. On the other hand 
there cannot be much doubt that the old part may have some influ- 
ence, and in certain cases a very important influence on the new part, 
but whether this is a purely molecular influence is open to doubt. In 
whatever way this influence may act, it is only one of a number of 
factors that take a share in the result. The amount of new material, 
that is formed before the organization of the new part begins, seems 
to be also a factor ; and the one that determines how much of the 
missing part can be replaced, and this in turn seems to be connected 
with the lowest organization size that can be produced. The distal 
end of the new part forms always the distal end of the organ that is 
to be produced. If enough new material has developed (before the 
organization of the new part takes place) to produce all of the miss- 
ing part, the latter is formed, but if the material is insufficient to pro- 
duce the whole structure, then as much of the distal end as possible 
is formed. In some cases, as in the planarians, the missing interme- 
diate regions may subsequently develop behind the distal part that is 
first produced. 

Sachs has advocated a view which has many points of similarity 
to that of Bonnet, although, in reality, it is not a theory of pre-forma- 
tion at all, but one of pure epigenesis. His idea rests on the view 
that the form of a plant, or of an animal, is the expression of the kind 
of material of which it is composed. Any change in its material 
leads to a corresponding change in the form of the new parts. 
Sachs holds that the idea of many morphologists, that there is for 
each organism a specific form that tends to express itself, and which 
controls the development of the organism, is a metaphysical idea that 
has no ground in science. For instance, Sachs thinks that the flower 
buds of a plant develop, not because of some innate, mystical force 

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266 REGENERATION 

that causes the plant to complete its typical form, but because some 
substance is made in the leaves which, being carried into the growing 
region, becomes there a part of the material of that region, and from 
this new material a flower is formed. Simple and clear as this 
hypothesis appears to be at first sight, it will be found on more care- 
ful examination that it fails to account for some of the most charac- 
teristic phenomena of development and of regeneration. It may be 
granted at the outset that the presence of certain substances may 
undoubtedly influence the kind of growth of a new part ; but, on the 
other hand, one of the most characteristic things of the organism is 
that it asserts its specific nature within quite a wide range of change, 
and, on the whole, resists the influence of other kinds of substances 
than those connected with its ordinary life. While Sachs looked no 
farther than the material substratum, and supposed that any change 
in this altered the form, there is, at present, sufficient evidence to 
show that it is the structure of the material that determines the most 
important changes that take place in it. This means, if we attempt 
to divest the statement of its somewhat metaphysical appearance, 
that the material of the organism is not simply a mixture of different 
kinds of materials, but a special kind of substance that has a definite 
structure of its own. This structure may, of course, be changed, but 
only by the addition of materials that the structure can take up as a 
part of itself. If the material does not become a part of the struc- 
ture or organization, it is without effect on the form.^ My meaning 
can, perhaps, best be illustrated by the method of regeneration of 
the tail of the fish from an oblique cut-surface. The growth of the 
new part is not determined by the kind or by the amount of the new 
material that is brought to the growing part, for, if it were, the new 
part would grow at an equal rate at every point ; but the growth of 
the new part is regulated by the form of the tail of each particular 
kind of fish. The structure of the new part controls the growth of 
the material of the new part, and not the reverse. The only inter- 
pretation that can be given to this result is, I believe, that the new 
material assumes a definite structure, or what we may call an organi- 
zation, and the subsequent changes are controlled by the kind of 
structure that is present ; and since this structure has, as a whole, a 
definite form, we can state that the form controls the material, 
although the substitution of the word **form" for that of **the structure 
of the new material " may give the statement an unfortunate, meta- 
physical appearance. 

In order to explain the regeneration of a piece of a plant, Sachs 
supposes that two substances are produced by the plant, — one a stem- 
(or leaf-) forming substance and the other a root-forming substance. 

^ Unless it produces a physical change in the structure. 

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THEORIES OF REGENERATION 26/ 

If either of these substances combines with the protoplasm of any part, 
a stem or a root is produced from that part. When a piece of the 
stem is cut from a plant, these two substances accumulate, one at the 
distal end and the other at the proximal end of the piece, and their 
presence in these regions determines that new shoots develop at or 
near the apex, and new roots at the base. Sachs tried to show that 
the direction of the flow of these two substances is determined by the 
action of gravity, — the lighter substance flowing to the higher parts, 
and the heavier to the lower parts. We find here reproduced Bonnet's 
idea of specific substances flowing in definite directions ; but Sachs 
goes farther, and gives an explanation of the cause of the different 
directions taken by the two kinds of substances, viz. that it is due to 
the action of gravity. Vochting has shown, as we have seen, after a 
thorough examination of the method of development of pieces of plants, 
that Sachs's hypothesis fails to account for the results ; and he shows 
also that an internal factor, which he calls the polarization, has the 
most important influence on the regeneration. 

It is not difficult to show that there are many other cases to which 
the stuff hypothesis does not apply. If, as Bonnet attempted to show, 
the regeneration is due to different stuffs, there is no explanation to 
account for the flow in animals of head-forming stuffs forward and 
tail-forming stuffs backward. In animals that regenerate laterally as 
well as anteriorly and posteriorly, we should be obliged to assume 
side-forming stuffs as well as head-forming and tail-forming stuffs ; 
and since the kind of structures that are produced at the side are 
different at each level, we should be obliged to assume that there are 
many kinds of lateral stuffs. If regeneration can take place in a 
dorsal and in a ventral direction, as, for example, when the dorsal and 
the anal fins of teleostean fishes regenerate, there must also be stuffs to 
account for their development. When regeneration takes place from 
an oblique surface, it must be supposed that two or more of these 
kinds of stuff are brought into action. The regeneration of just as 
much of the limb of the salamander as is cut off also offers difficulties for 
Sachs's view. If we assume a leg-forming substance, it fails to account 
for the difference in the result at each level. If we assume that 
different substances come into play according to the amount of the leg 
that has been cut off, the hypothesis becomes as complicated as the 
facts that it pretends to explain. 

A special case, to which the stuff hypothesis has been applied by 
Loeb and by Driesch, is that of tubularia, although the latter writer 
has used the hypothesis only to a limited extent as involving quanti- 
tative rather than qualitative results. There is present in the hydranth 
and stem of tubularia a red pigment in the form of granules in the 
endodermal cells. There is more of the red pigment in the stem near 

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268 REGENERATION 

the hydranth than elsewhere. If a piece of the stem is cut off, it 
closes its cut-ends, and a circulation of fluid begins in the central cavity. 
In this fluid globules now appear that contain the red-pigment granules. 
The globules appear to be free endodermal cells, or parts of such, that 
have been set free in the central cavity. In the course of twenty-four 
hours the new hydranth begins to appear near one end of the stem, 
and in this region of the stem a much larger number of granules ap- 
pear. A little later all the red granules disappear from the circulation. 

Driesch has supposed that the red granules of the circulation be- 
come a part of the wall of the new hydranth. The disappearance of 
the red granules at this time from the circulation would seem to give 
color to this view. But, on the other hand, I have found evidence 
showing that this interpretation is incorrect In the first place, the 
granules that disappear from the circulation can be found lying in a 
ball within the digestive tract of the newly formed hydranth ; hence 
their disappearance can be accounted for, and we find that they are 
not, or at least in large part are not, absorbed into the forming hy- 
dranth.i In the second place, there is a great increase in the number 
of endodermal cells in the region in which the hydranth is about to 
appear, and the thickening that results takes place some time before 
the granules begin to disappear from the circulation. The new gran- 
ules appear in the new endodermal cells, and are presumably formed 
by them. Again, the hydranth, that develops later at the distal end, 
appears when there are no granules in the circulating fluid, and yet 
the hydranth may contain as much red pigment as does the proximal 
one. Lastly, the development of very short pieces shows that at the 
time of the formation of the new hydranth there is an enormous in- 
crease in the number of red granules in the piece, for there are many 
more of them contained in the new hydranth than were present in the 
entire piece at the time of its removal. 

Loeb has not referred to the red granules in the circulating fluid, 
but simply to the red pigment which is present in the walls of the 
piece. This is supposed to move forward into the hydranth region, 
and call forth the development of a new hydranth. A study of the 
number of the granules in the stem gives no support to this idea, 
and the method of formation of single and of double hydranths in 
short pieces shows that the increase in the number of granules in 
the hydranth-forming region is not due to migration, but to local 
formation. 

That specific substances may have an influence on the growth of 
certain parts cannot be denied, but it appears that in general they 
play a very secondary rdle as compared with other factors that 

1 Stevens ('oi) has found that this ball of red pigment is ejected from the mouth of the 
new hydranth. 



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THEORIES OF REGENERATION 269 

determine the form of the organism or the development of a part. 
Vochting's beautiful experiments ('86) on tuberous plants show that 
the presence of an excessive amount of food substances in the plant, 
brought about by the artificial removal of the natural storehouses for 
3uch material, may act on certain parts, such as the axial buds, or on 
the stem, and cause them to produce structures that they do not pro- 
duce under ordinary circumstances. The axial buds become swollen 
and produce tuber-like bodies above ground, especially if the parts 
are enclosed so as to be in the dark, since the light retards the growth 
of tubers of all sorts. But it should not be overlooked that these 
buds and stems are structurally the same things as the tuberiferous 
stolons that have been removed, and hence the excess of material is 
stored up in them in the same way as it is under normal circumstances 
in the underground stems or stolons. The reaction is one normal to 
the plant, although it usually takes place in a different part. 

The preceding hypotheses that have been advanced to account 
for the phenomena of regeneration, draw attention to some of the 
most fundamental problems of regeneration and, even in those cases 
in which the hypotheses have not given a satisfactory solution of the 
problems, some of them have served the good purpose, both of direct- 
ing attention to important questions and of leading biologists to make 
experiments to test the new points of view. We should not underrate 
their value, even if they have sometimes failed to give a solution of 
problems, for they have been useful if only in eliminating certain 
possibilities, and this simplifies all future work. So long as an 
hypothesis is of a sort that it is within the range of observational and 
experimental test, it may be of service, even if it prove erroneous ; 
for our advance through the tangled thread of phenomena is not only 
assisted by advances in the right direction, but all possibilities must 
be tested before we can be certain that we have discovered the whole 
truth. The value of a scientific hypothesis depends, it seems to me, 
first, on the possibility of testing it by direct observation, or by experi- 
ment; second, on whether it leads to advance; and, lastly, on its 
elimination of certain possibilities. 

The experiments described in Chapters II, III, IV, have shown that 
there are many resemblances between the phenomena of growth and 
of regeneration. It has been pointed out that when it could be shown 
that certain external agents have a determining influence upon growth, 
these same agents have a similar effect upon regeneration. This 
also holds apparently for internal factors, although it is much more 
difficult to demonstrate that this is true. The presence of an abun- 
dance of food material in the tissues hastens regeneration in the same 
way that growth is more rapid in a well-fed organism. Food may, 
however, be looked upon rather as an external factor than as an 

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270 REGENERATION 

internal one. An excellent example of an internal factor is found in 
the interrelations of the parts to each other. This is shown in the 
development of a piece of a plant in which the apical buds develop 
faster than the proximal ones, and it appears that, in some way, the 
development of the latter are held in check by the development of 
the apical ones. Another case is found in the development of the 
bilobed tail of certain fish in which particular regions are held in 
check, while others grow at the maximum rate. 

It is a curious fact that while we can cite several kinds of external 
influences that affect the development and the regeneration of organ- 
isms, the only internal factors that have been discovered are the so- 
called polarity and this interrelation of the parts. Perhap" there 
should also be added the specific nature of certain parts, limiting 
the possibilities of new growth in these parts, and the presence 
of the nucleus as necessary for the growth and regeneration of the 
organism. 

If it be admitted that the same factors that affect the growth also 
affect in the same way the regeneration, we have made a distinct 
advance. It is, moreover, not difficult for us to understand how this 
is possible. If we consider first those cases in which growth takes 
place at one or more points at which the cells are undifferentiated, 
and compare this condition with that in regenerating animals that 
produce new tissue by proliferation, we can picture to ourselves 
that the same factors would act on the undifferentiated tissue in the 
same way in both cases. This does not explain what causes the 
organism to produce the new cells that appear over an exposed sur- 
face, and we must search for other factors to account for the out- 
wandering of cells, and for the local multiplication of the cells at the 
cut-end. We find a parallel to those cases in which the growth of 
an organism takes place throughout the whole body, in those animals 
in which the regeneration also takes place in the old part. This com- 
parison should not, however, be pushed too far, since, in some forms, 
as, for example, a salamander, the growth of the animal takes place 
throughout the body, while regeneration takes place by the prolifera- 
tion of new material. The difference in the regenerative process in 
a salamander and in a form like hydra is not due so much to the 
inability of the old cells of the salamander to increase in number as 
compared with those of hydra, but rather, it appears, to a certain 
rigidity or stiffness of the body of the salamander that prevents the 
rearrangement of the parts ; and the recompletion of the form takes 
place in the direction of least resistance, i,e. at the open or cut-end 
of the body. 

Regeneration by means of morphallaxis takes place only in those 
forms in which the body is not made up of a series of separated 

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THEORIES OF REGENERATION 27 1 

parts. This kind of regeneration occurs in those organisms in 
which the normal growth consists only in the enlargement of a sys- 
tem of organs already present. A piece of an animal of this sort 
usually contains the elements of each kind of organ, and from these 
the new parts are produced, both by proliferation at the cut-ends and 
by the enlargement of the parts that are present in the piece. In 
forms with separate segments we find, in some cases, resemblances 
between normal growth and regeneration, as shown, for example, 
in the earthworm. There is present in the young worm a region in 
front of the last segment, or, rather, a part of this segment, from 
which new segments are formed. In the regeneration of the posterior 
end a knob of new tissue is formed, and out of this a few segments 
develop, the last one having a growing region similar to that in the 
young worm. The subsequent stages in the regeneration involve 
the formation of new segments from the last one, as in the young 
worm. There is no such growing zone at the anterior end of the 
young worm, and none is formed in the regeneration of an anterior 
end, so that only the segments that are first laid down in the new 
part are present in the new anterior end. 

An interesting comparison may be made between the phenome- 
non of growth and that of contraction and expansion of the proto- 
plasm. The bending of heliotropic organisms toward or away from 
the light, and the similar bending of negatively stereo tropic forms 
away from contact with a solid body, are supposed to be phenomena 
of growth, and resemble in many ways the phenomenon of contrac- 
tion. In a plant that bends toward the light, it is found that the 
most obvious change involves the amount of water on the two sides 
of the stem, and this is most probably connected with a fundamental 
structural change in the protoplasm, that is too subtile for further 
analysis. In the regeneration of some forms it is found that they re- 
spond in the same way to light. While it cannot be demonstrated 
that these phenomena really depend on processes of contraction 
and of expansion, the results are nevertheless suggestive from this 
point of view. Furthermore, I think, one cannot study the regenera- 
tion of such forms as planarians, hydras, stentors, etc., without being 
struck by the apparent resemblance of the change in form that they 
undergo to a process of expansion. The idea of the expansion of 
a viscid body carries with it, of course, the idea of tension within the 
parts, and the return to the former condition is brought about by a 
release from the tension and a return to a more stable condition. 
If by the intercalation of new material the extended condition is 
fixed, a new state of equilibrium will be established. 

It has been already pointed out that in a piece of a plant suspended 
in a moist atmosphere, the apical buds are those that first develop. 

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2/2 REGENERATION 

and also grow faster than the others. The buds situated nearer the 
base may not even begin to develop, although they are at first as 
favorably situated, so far as external circumstances are concerned, as 
the uppermost ones. The roots appear first over the basal end, 
and those nearer the base grow faster than do those nearer the 
apex. There cannot be much doubt that the suppression of the 
basal buds and of the more apical roots is connected with the devel- 
opment of the apical buds and of the basal roots. This can be 
shown by cutting a piece in two, when some of the basal buds will 
grow into shoots and the apically situated root-buds, that are 
now on the base of one piece, will begin to grow. It seems to me 
this relation can be at least more fully grasped, if we look upon it as 
connected with some condition of tension in the living part. The 
tension can be thought of as existing throughout the softer, more 
plastic parts. As long as the apical bud is present at the end of a 
stem or branch, or even near the apex, it exerts on the parts lying 
proximal to it a pull, or tension, that holds the development of these 
parts in check ; but if the apical bud is removed the tension is relaxed, 
and the chance for another bud developing is given. 

It may be asked, how can it be explained that only the more api- 
cally situated buds of a piece develop, rather than the basal ones, 
since with the removal of the piece from the plant the tension has 
been removed also. The only answer that can be made, so far as I 
can see, would be that from the apex of the plant to its base the ten- 
sion is graded, being least at the apex and increasing as we pass to 
the base. Those buds will first develop that are in the region of least 
tension, and their development will hold in check the other buds by 
increasing or reestablishing the tension on the lower parts of the 
piece. A new system is then established, like that in the normal 
plant. 

There are certain experiments with hydra that can, perhaps, be 
brought under the same point of view. When two long posterior 
pieces are united by their anterior cut-surfaces, each piece regener- 
ates a circle of tentacles near the region of union, and each may pro- 
duce a new head; or only one head, common to both pieces, develops 
at the side. Each piece has retained its individuality, which may 
be interpreted to mean that each piece has retained its original con- 
dition of tension. If, however, after a union of this kind one piece is 
cut off, as soon as the two have well united, near the place of union, 
so that it is relatively small as compared with the other component, 
it may produce a head at its exposed basal end, and neither heads 
nor tentacles may develop at the place of union of the pieces. 

It is probable, in this case, that the larger component has acted 
on the smaller one, so that its polarity is changed and becomes like 

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THEORIES OF REGENERATION 273 

that of the larger component. It is possible, I think, to interpret 
this result in terms of our tension hypothesis. The condition of ten- 
sion in the larger piece has overcome that of the smaller piece, so 
that the latter comes to have the same orientation that the larger piece 
has ; and the development of a head at the free end then takes place. 
The development of this head holds in check the development of a head 
at the anterior end of the larger piece in the region of union of the 
pieces. When two pieces of hydra are united by unlike poles, i.e, so 
that they have the same orientation, it is found that if the pieces are 
not too long, a head develops at the free end and none in the region 
of grafting. The result is similar to that in plants ; the development 
of the head at the free end suppressing any tendency that may exist 
to produce a new head by the posterior piece at the place of union. 
If the pieces united in this way are very long, a head develops at the 
apical end, and, in some cases, also near the line of union. This may 
be due to the pieces being so different at the place of union, that 
a head develops below this region before the unification of the two 
pieces is brought about, or because the formation of the head at 
the free end is relatively so far removed from the place of union of 
the pieces, that it does not influence the development of a head in 
this region. 

These cases of grafting also illustrate another point of some 
interest. They show that the development of a head at the anterior 
end of a piece is not the result of the injury from the cutting or 
due to the action of some external condition on the free end, for 
the regeneration may take place when two anterior ends have been 
perfectly united to each other. The result can only be explained as 
the outcome of some internal factor such as polarity. 

These examples have been chosen from hydra rather than from 
tubularia, in which somewhat similar phenomena have been observed, 
because in hydra the development of heteromorphic structures is of 
rare occurrence, while in tubularia external influence often calls forth 
a heteromorphic development. There cannot be much doubt, how- 
ever, that in tubularia the same kind of internal factors are also at 
work. 

A more striking illustration of the possible influence of tension of 
the parts is shown by an experiment with planarians. If the head 
of a planarian is cut off and the posterior piece is split partially in 
two along the middle line, as shown in Fig. 31, A, and then one of 
the halves is cut off just anterior to the end of the longitudinal cut, 
the result is as follows : A new head develops at the anterior end 
of the long half (Fig. 31, B\ but no head develops on the posterior 
cut-surface, provided this part -has reunited along the middle line 
with the long half, and a line of new tissue connects the anterior 

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274 REGENERATION 

cut-surface of the long half and the more posterior cut-surface of the 
shorter half. At least this happens if the piece is not split too far 
posteriorly, i,e, through the region of the pharynx. If this is done, 
a new head may develop from the posterior cut-surface. In another 
way the development of the more posterior head can be brought 
about. If the shorter side-piece is kept from fusing with the longer 
side-piece in the middle line, it will invariably produce a new head 
(Fig. 31, Cy The lack of development of the posterior head, when 
the two cross-cut surfaces are united by a connecting part of new 
material, can, it seems to me, be best explained by the influence of 
the developing anterior head, or of the new side on the posterior new 
tissue, and this influence can, I think, be better appreciated if we 
suppose some sort of tension to be the influence at work. 

Another example may be cited that shows even more clearly that 
the internal factor regulating the growth in the new part is probably 
some sort of tension. I refer to the development of the tail of 
fundulus from an oblique cut, or of the bilobed tail of stenopus from 
a cross cut. The assumption of the typical form that leads to the 
holding in check of the growth in certain regions, as compared with 
others, can be best understood, I think, as due to some sort of ten- 
sion established in the different parts, that regulates the growth in 
those regions. 

It is evident that whatever factor will serve to explain the preceding 
cases must also be expected to apply to the development of the whole 
embryo from parts of the ^gg or blastula, if the position that I have 
taken is correct, namely, that these phenomena belong to the same 
general group. Does the tension hypothesis make clearer the devel- 
opment of a whole embryo from a part of an egg } This means, can 
we think of the readjustment that takes place as due to the establish- 
ment of a characteristic equilibrium that expresses itself in the 
tensions of the different regions } There is, so far as I can see, no 
difficulty in supposing that the organization is at bottom a system of 
this kind ; indeed, it seems to me that from this point of view we can 
get a better appreciation of the organization and of the series of 
changes that take place in it during development. The example that 
Driesch has chosen as a typical one of vitalistic action, namely, the 
proportionate development of a part of the archenteron of the half- 
embryo, seems to me to be likewise a case to which we can apply the 
tension view. 

s In these, as well as in all other cases, we must think of the ten- 
sions as existing, not only in one direction, but in the three dimensions 
of space, and of all combinations of these. The material in which 
the tensions exist must be thought of as labile, so that a change in 
one region involves a rearrangement in many cases of the entire sys- 

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THEORIES OF REGENERATION 2/5 

tem. The new rearrangement appears to take place on the founda- 
tions of the old system. 

It may appear that this idea of a system of tensions is too vague, 
that it fails to point out how the reorganization takes place, and that 
it gives not much more than the facts do themselves. There is a 
certain amount of truth in these objections which I fully appreciate, 
but something further can be said on these points. The view is 
vague in so far as we cannot picture to ourselves in a mechanical 
way just how such a system could bring about the suppression of 
growth in one region and allow the maximum amount in another 
region. But this is asking too much, since the hypothesis can only 
claim, at present, to furnish a means by which we can at least 
imagine what sort of a process is involved, and cannot give the 
details of the process itself. It can be shown experimentally that if 
the phenomenon is one of tension certain results should follow that 
are observed to take place, as when by keeping the shorter half of 
the planarian from reuniting to the larger half, or by breaking the 
union if it has been formed, a head develops also at the posterior 
cross-cut. In the second place, although we cannot understand how 
the rearrangement of the tensions in a piece takes place, yet from 
a causal point of view we can see how a change in one region of a 
labile system may produce, by means of a change of tension, a com- 
plete rearrangement of the parts throughout. It can even be 
claimed for the tension hypothesis that it at least becomes easier for 
us to see how such a change could take place, because it represents 
the organization as the expression of a system under tension, and 
hence, if the material is sufficiently flexible, a readjustment will proba- 
bly take place when the system is changed in any region. It enables 
us to see how the organization of the egg may be divided by every cell 
division, and yet after the reunion of the cells the original equilibrium 
be established. We may perhaps claim, therefore, that in these re- 
spects the hypothesis does give us something more than do the 
facts ; and, inasmuch as it brings a large number of phenomena under 
a common point of view, the idea may be worth further consideration. 

In conclusion, I may add that the hypothesis is, I hope, also a legit- 
imate one, in the sense that being within reach of an experimental proof 
or disproof, it may serve at least as a working hypothesis. Per- 
haps more fundamental than the idea that a system of tensions 
exists throughout the organization is the conception that the organi- 
zation is itself a system of interrelated parts, and not a homogeneous 
substance or a mass composed of a large number of repeated parts, 
or rather, despite the presence of smaller, repeated units, the organi- 
zation is not the result of their interaction, but of their regular 
arrangement as parts of a whole structure. If, then, this^ inter- 
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276 REGENERATION 

relation of the different parts of the structure can be looked upon- as 
the result of a system of tensions, we can at least form a better idea 
as to how a piece of a whole can readjust itself into a new whole of 
smaller size. And it is this possibility of rearrangement or regula- 
tion that is one of the most characteristic properties of living things. 



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CHAPTER XIV 
GENERAL CONSIDERATIONS AND CONCLUSIONS 

In the preceding chapters certain matters had to be taken for 
granted, since it was not possible, or desirable, at the time to discuss 
more fully some of the terms that are in common use, or to analyze 
more completely many of the phenomena. It was also not necessary 
to give the general point of view under which the phenomena were 
considered in their physical, chemical, or even causal connection. 
Little harm has, I trust, been done by relegating such questions to 
the final chapter. An attempt will now be made to give more explicit 
statements in regard to the use and meaning of such terms as " organi- 
zation,** "polarity,** "factors,** "formative forces,*' " vitalistic** and 
"mechanical principles,** "adaptation,** etc. 

It will be found that the hypotheses that have been advanced to 
account for the phenomena of development and of regeneration may 
be roughly classified under two heads : first, those in which the organi- 
zation is " explained *' as the result of the collective action of smaller 
units ; and second, those in which the organization is itself regarded 
as a single unit that controls the parts. Let us examine these points 
of view more in detail, in order to see what has been meant in each 
case by " the organization." 

A favorite method of biological speculation in the last forty years 
has been to refer the properties of the organism to invisible units, 
and to explain the action of the organism as the resultant of their 
behavior. The hypothesis of atoms and of molecules, by means of 
which the chemist accounts for his reactions, has proved so exceed- 
ingly fruitful as a working hypothesis that it has had, I think, a 
profound influence on the mind of many biologists, who have, con- 
sciously or unconsciously, attempted to apply a similar conception 
to the structure of living organisms. The discovery that all of the 
higher organisms are made up of smaller units, the cells, and that 
the lower organisms are single, isolated cells, comparable to those 
that make up the higher forms, has also drawn attention to the idea 
that the whole organism is the result of the action of its units. Fur- 
thermore, within the cells themselves units of a lower order have also 
been discovered, such, for instance, as the chromosomes, the chloro- 

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278 HE GENERA TION 

phyl bodies, etc., that repeat on a smaller scale some of the 
fundamental properties of the entire organism, as growth and divi- 
sion. It has been assumed that still farther down in the structure 
there are smaller units having the same properties, and the smallest 
of these are the ultimate units. The organism is looked upon as the 
result of the properties of these minute germs. The gemmules of 
Darwin furnish an example of an hypothesis of this sort; also the 
intracellular pangens of De Vries, the plasomes^of Wiesner, the bio- 
phors of Weismann, the idiosomes of Hertwig, and the micellae of 
Nageli are other examples of this way of interpreting the organization. 
These elements are endowed by their inventors with certain properties, 
and these are of such a sort that they give the appearance of an explana- 
tion to organic phenomena, lit is useless to object to these hypotheses 
that they are purely ideal, or fictitious, and that those properties have 
been assigned to the germs that will bring about the desired explana- 
tion, and have not been shown to be the real properties of the germs 
themselves. But apart from the arbitrariness of the process, it cannot 
be claimed that a single one of these creations has been shown to be 
true, or has even been accepted by zoologists as probable. A more 
serious objection to this point of view is thatfthe most fundamental 
characteristics of the organism, those that concern growth, develop- 
ment, regeneration, etc., seem to involve in many cases the organism 
as a whole.; So many examples of this have been given in the preceding 
pages, that it is not necessary to go over the ground again. It has 
been shown that a change in one part takes place in relation to all 
other parts, and it is this interconnection of the parts that is one of the 
chief peculiarities of the organism. In phenomena of this kind even 
the cells seem to play a secondary part, and if so, we can, I think, 
safely leave out of account the smaller units of which the protoplasm 
is supposed to be built up and we can neglect them, if for no other 
reason than this, that the argument that has called them into existence 
starts out with the cell as the highest unit. If the cell can be thrown 
out, most probably the units of which the cell itself is supposed to be 
made up can be safely disregarded also. 

It may be objected that only through a knowledge of the minute 
structure of the organism can we hope to understand the behavior of 
the whole ; but my point of view is not that there may not be a funda- 
mental structure, but that this is no.t formed by a repetition of ele- 
ments, which give to the whole its fundamental properties. It can be 
shown, I think, with some probability that the forming organism is of 
such a kind that we can better understand its action when we con- 
sider it as a whole and not simply as the sum of a vast number of 
smaller elements. To draw again a rough parallel; just as the 
properties of sugar are peculiar to the molecule and cannot be ac- 

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GENERAL CONSIDERATIONS AND CONCLUSIONS 2/9 

counted for as the sum total of the properties of the atoms of carbon, 
hydrogen, and oxygen of which the molecule is made up, so the prop- 
erties of the organism are connected with its whole organization and 
are not simply those of its individual cells, or lower units. 

The strongest evidence in favor of this view is found in the 
behavior of small pieces of an egg, or of a protozoon, or even of a 
many-celled organism. A lower limit of organization is very soon 
reached, below which the piece fails to produce the characteristic 
form, although all the necessary elements are present in the piece to 
produce the entire structure. The size of these pieces is enormously 
large as compared with the size of the cell, or of the imaginary ele- 
ments of Nageli, Weismann, Wiesner, etc. These results indicate 
that the organization is a comparatively large structure. 

A few writers have either ignored the presence of smaller units, 
or have dealt with the organism from a purely chemical and physical 
point of view. They attempt to account for the changes in the 
organism as the outcome of known physical and chemical princi- 
ples. It must, of course, be granted that in a sense the properties 
of the organism are the result of the material basis of the organism ; 
but in another sense this idea gives a false conception of the 
phenomena of life, becauselif we were simply to bring together those 
substances that we suppose to be present in the organism we have no 
reason to think that they would form an organism, or show the 
characteristic reactions of living things.^ Even from a chemical point 
of view we can see how this result could not be expected, for it is 
well known that the order in which a compound is built up, i.e, the 
way in which the atoms or molecules are introduced into the structure, 
is an important factor in the making of the compound. When we re- 
member the immense period of time during which the organisms living 
at present have been forming, we can appreciate how futile it will be 
to attempt to explain the behavior of the organism from the little we 
know in regard to its chemical composition. Its chief properties 
are the result of its peculiar structure, or the way in which its ele- 
ments are grouped. This structure has resulted from the vast num- 
ber of influences to which the organism has been subjected, and 
while it may be granted that if we could artificially reproduce these 
conditions an organism having all the properties that we associate 
with living things would result, yet the problem appears to be so 
vastly complicated that few workers would have the courage to 
attempt to accomplish the feat of making artificially such a structure. 
To prevent misunderstanding, it may be added that while from the 
point of view here taken, we cannot hope to explain the behavior 
of the organism as the resultant of the substances that we obtain 
from it by chemical analysis (because the organism is i^9^^WPJK> 

y y ^\ 



280 ~ REGENERATION 

a mixture of these substances), yet we have no reason to suppose that 
the organism is anything more than the expression of its physical and 
chemical structure.^ The vital phenomena are different from the 
non-vital phenomena only in so far as the structure of the organism 
is different from the structure of any other group of substances. 

< Nageli has stated that each part acts as though it ktiew what the 
other parts are doing. His idea of the idioplasm involves a con- 
ception of the organism as a whole and not simply the sum total 
of a number of parts. Hertwig, who maintained at one time that 
the development of the embryo is the resultant of the action of the 
cells on each other, admits i^ his work on Die Zelle und die 
Gewebe that while this is in part true, yet on the other hand the 
whole also exerts an influence on its parts. Driesch, who hypotheti- 
cally suggested at one time that the nuclei act as centres of con- 
trol of the cell by means of enzymes, has later adopted a widely 
different view. Whitman has made a strong argument to the effect 
that the cell theory is too narrow a standpoint from which to 
treat the organism, and on several occasions I have urged that the 
organism is not the sum total of the action and interaction of its 
cells, but has a structure of its own independent of that of the cells. 

This discussion will suffice to show some of the opinions that have 
been held as to the nature of the organization of the organism. Let 
us next ask what properties we may ascribe to it. 

It has been found that certain polar, or rather dimensional, rela- 
tions are characteristic of the organization. The term "polarity" ex- 
presses this in a limited way, but refers only to one line having 
two directions, while we now know that the dimensional properties 
relate to the three dimensions of space, and for this idea we might 
make use of the term heterotropy. Thus we find that a piece of 
a bilateral animal regenerates a new anterior end from the part that 
lay nearer the anterior end of the original animal, a new right side 
from the part that was nearest the original right side, and a new 
dorsal part from the region that lay near the original dorsal 
part, etc. 

The polarity of a part can be changed in certain forms, as in 
tubularia, by exposing the posterior cut-end to the external factors 
that bring about the formation of a hydranth, or, as in hydra, by 
grafting in a reversed direction a smaller piece on a larger one. In 
Planaria Itigubris and in the earthworm the polarity of the new 
tissue may be reversed, as compared with that of the part from which 
it develops, if the new part arises from certain regions of the body. 
A curious instance of the effect of the polarity is shown by the regen- 
eration from an oblique surface in planarians. The new head arises 
from the more anterior part of the new material, rather tton frona the 

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GENERAL CONSIDERATIONS AND CONCLUSIONS 28 1 

middle of the anterior oblique surface, and the new tail arises from 
the more posterior part of the posterior oblique surface. As an analy- 
sis of this result has been already attempted in an earlier chapter, it 
will not be necessary to go further into this question here. 

The development of a new part at right angles to an oblique sur- 
face has also been described, and it has been pointed out that the 
result appears to be due to the symmetrical development of the new 
structure in the new part. This symmetry of the newly forming part 
must be also counted as one of the properties of the organization. 

Finally, the mode of regeneration of a new, bifurcated tail in the 
teleost, stenopus, shows that the new part may very early become 
moulded into the characteristic form, and that the growth of the 
different parts is regulated by the structure assumed at -an early 
stage. The new part does not grow out at an equal rate until it 
reaches the level of the notch of the old tail, and then continue to 
grow at two points to produce the bilobed form of the tail; but 
the bilobed condition appears at the very beginning of the develop- 
ment. 

These illustrations give us nearly all the data that we possess at 
present on which to build up a conception of the organization. That 
we must fail in large part fully to grasp its meaning from these meagre 
facts is self-evident. The main difficulty seems to,- lie in this, — that 
^hen we attempt to think out what the organization ^is we almost un- 
avoidably think of it as a structure having the properties of a machine, 
and working in the way in which we are accustomed to think of ma- 
chines as working.; The most careful analysis of the "machine 
theory," as applied to the phenomena of development and of re- 
generation, has been made by Driesch. It has been pointed out that 
in his Analytische Theorie Driesch assumed that development is due 
to " given *' properties in the egg ; that each stage is initiated by some 
substance contained in the ^gg acting on the stage that has just been 
completed. That is, each stage is the condition of the following. 
The ** rhythm" of development is accounted for in this way. The 
changes are described as due to chemical processes (including also 
ferment actions). The nucleus is supposed to contain all the different 
kinds of ferments that act, when set free, as stimuli on the protoplasm ; 
but since the ferments are always set free at the propitious moment, 
Driesch was obliged to assume that the cytoplasm acts on the nucleus 
in such a way as to make it produce the proper ferment for the next 
stage. Thus the cytoplasm first influences the nucleus, the latter 
sets free a specific ferment that starts a new chemical change in the 
cytoplasm, and the changed cytoplasm may then react again on the nu- 
cleus, and a different ferment be set free, etc. Each change is there- 
fore not only an effect of what has gone before, but the cause of the 



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282 REGENERATION 

next process.^ Driesch points out that it is necessary at this stage to 
make a further assumption, because the cytoplasm must not only be 
acted upon by the ferment, but it must itself be of such a sort that it 
responds to the action. This leads to a great complication of the 
phenomena ; but the assumption does not depart, in the last analysis, 
from the idea of the cell as a system in a mechanical sense. This 
assumption of a receiving and an answering station for the stimuli 
carries with it the further assumption of a many-sided '' harmouy."' 
Without a harmony at each step in the development there could be 
no orderly ontogeny. The assumption of this harmony introduces a 
new element into the series of hypotheses. The appearance of a causal 
explanation was given in those parts of the argument preceding the 
introduction of the assumption of a harmony, but with the admission 
of this new element into the argument, the causal point of view is left. 
Driesch says in this connection : ** If we cannot gain a singleness of 
view in the way that has been followed, we can reach this in another 
way. Indeed, the way of doing so has been already implied in that 
part of the theory dealing with the harmony of the phenomena. The 
existence of this harmony is inferred, because, in the large majority of 
cases, the ontogeny leads to a typical result. Therefore we must 
assume that the conditions for the end result are given — the con- 
ditions are the harmony itself." Put somewhat less obscurely, if more 
crudely, we may express Driesch's idea by saying that the harmony 
that stands for a hen is given in the hen's egg. 

Driesch adds : " Because a typical result always follows, therefore 
every single step in the ontogeny must be judged, from an analytical 
standpoint, from the point of view of the result itself. The result is 
Wit purpose of the ontogeny. It is as though we visited daily a wharf 
where a ship is being built, — everything appears a chaos of single 
pieces, and we can only understand what we see when we consider 
what is to be made. Only from a teleological point of view can we 
speak of a development, for this term expresses the very existence of 
an object to be developed. The term is used fraudulently if it is 
intended to mean that the development is the outcome of * processes,' 
using this term in the sense that a mountain or a delta develops from 
physical processes." " We can only reach a satisfactory view of the 
phenomena when we introduce the word 'purpose.* This means that 
we must look upon the ontogeny as a process carried out in its order 
and quality as though guided by an intelligence. We arrive at this 
conclusion, because the individual whole is 'given,' as the clearly 
recognized goal of the entire process of development." 

^ The importance of this conception is, in my opinion, marred by the fiction of the ferment 
action of the nucleus; but it should not be overlooked that Driesch avowedly called this a 
pure fiction. 



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GENERAL CONSIDERATIONS AND CONCLUSIONS 283 

In a later attempt to analyze the problem of development, Driesch 
examined it more fully from the point of view of the machine theory. 
This contribution must be looked upon rather as a tour de force that is 
intended to show how far this idea can be carried in its application 
to development. Driesch explains that in his analytical theory he 
assumed from what is " given " in the egg that the egg can be under- 
stood causally, as a machine is understood, but what is "given " can 
be understood only teleologically. He says : " What I defended was 
not vitalism, but, so far as the phenomena of life are concerned, 
exactly the current physico-chemical dogmatism ; but I did not fail to 
see and to point out the consequences of this dogmatism, which every 
one (except Lotze) has avoided, viz., that the adaptive basis in which 
the living phenomena take place is 'given.'" Driesch defines his 
view as formal-teleological, in contrast to vitalistic. The former may 
also be called a machine theory of life in which the purpose is given^ 
not explained. 

In later writings Driesch has thrown over some of his earlier con- 
clusions and adopted a causal-vitalistic philosophy. The basis of this 
new conception is found in the proportional development of parts of 
an original whole, as has been explained in a preceding chapter. 
This result belongs to a category of phenomena that is in principle 
not machine-like, but of a specifically different kind. It is something 
that cannot be explained by the agencies of the outer world, such as 
light, gravity, salinity, temperature, etc. After examining other 
hypotheses, Driesch returns to a view that he had previously re- 
jected, viz. the conception of "position," by which is meant the influ- 
ence of the location in the whole. This position has certain directions, 
but nothing in addition that is typical. By the term " location in the 
whole " is meant that the word "location" {Lage) shall refer not to ge- 
ometric space, but to the organization of the object that has its own 
directions. A deformation of the whole may change very little the 
relative location of the parts. 

In his earlier writings Driesch rejected this idea, because it did 
not seem to satisfy our etiological need, and also because he thought 
that he could reach his goal from the standpoint of initiating stimuli 
{Auslosungen), Driesch now assumes that the stem of tubularia and 
the archenteron of the starfish, for example, have a polar structure. 
Bilateral forms, as the whole larva of the starfish, have a coordinated 
system of two axes with unlike poles and one axis with like poles, 
each of a given length or proportion. The ends of the axes are char- 
acteristic points of the system. If, in such a system, a typical act of 
differentiation appears, to which we can assign a cause, so far as the 
location is concerned, a change will occur as follows : To take the 
simplest case, that of a system with only one axis having unlike poles, as 

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284 REGENERATION 

the archenteron of the starfish, in which differentiation has not begun, 
we can picture to ourselves the formation of the divisions of the archen- 
teron in a causal way by supposing the end of the axis, or pole, to be 
the location {^Sits) of an initiative " action at a distance '* {aiislosende 
Fernkraft), This locality, just because it is the end of a system, 
is something special ; and it acts in such a way that wherever an effect 
is produced, it is the cause of that effect. This very way of looking 
at the problem postulates a sort of causal harmony. But how, it may 
be asked, can a special point or pole of an axis bring about an action 
in the system ? This can be shown by means of a simple case, viz. 
the dividing up of the archenteron of the starfish into its character- 
istic parts. There are two effects produced, viz. the formation of the 
two constrictions of the wall. We need not consider the fact that the 
constrictions are formed, for this is established in the potence of the sys- 
tem, and is awakened by the initiating cause, but the place at which 
the constrictions are produced is that for which we should account. 
We must think of this cause as "action at a distance," and indeed as 
an " action at a distance " that works at a determinate, typical dis- 
tance. This inherent measure of distance of the action is not one of 
absolutely fixed size, for a gastrula made shorter by an operation also 
subdivides into proportionate parts. The action starts from the poles 
of the system, and acts, not at an absolute, but at a relative distance, 
since it is dependent upon the length of the axis of the whole differ- 
entiating system. "The localization of ontogenetic processes is a 
problem S7ii generis. The phenomenon can always be expressed on 
the scheme of cause and effect, if we assume the 'action at a dis- 
tance' to start from fixed points of a differentiating system." 

In regard to the criterion of vitalistic phenomena Driesch makes 
the following statement : " On the current view we are inclined to 
see, in the formative changes, actual causes at work that even initiate 
those processes that we call stimuli ; we do so because we pretend at 
present to know something of the special mechanism by which the 
formative changes work. The effects come into play through a 
causal union of simple processes of a physical-chemical sort that we 
may call a chain of stimuli. From the new point of view, the initia- 
tory stimulus is not an initiatory cause or the effect of a causally 
united chemico-physical phenomenon. The stimulus is, from this 
point of view, a true stimulus, but the effect is not a true effect of 
its initiation, but is rather to be designated a responsive effect, for 
there is no connecting chain of stimuli. It is in the place of the 
latter that the vitalistic view appears. The only data of a machine 
sort in the conception are the arrangements for the reception and 
guidance of the stimulus, perhaps also the means for carrying out 
the response effect; for the machine data are only the prerequi- 

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GENERAL CONSIDERATIONS AND CONCLUSIONS 285 

sites of the phenomena, but in themselves do not bring about the 
result." 

Driesch finds in this argument a demonstration of the vitalistic 
doctrine, but vitalism, of course, of a very special kind. Without a 
more elaborate presentation of his view it is not possible to give a 
detailed criticism of his conclusions ; but a few of the more obvious 
objections that may be brought against this view may be discussed. 
The assumption of "action at a distance" does not, I think, in any 
way help to make the phenomenon clearer. The formation of a 
typical larva of normal proportions from a piece of an ^gg is just as 
mysterious after the assumption of an ''action at a distance" of a 
proportionate sort as it was before. Driesch has introduced into the 
argument to establish a vitalistic standpoint one of the most obscure 
ideas of physical science. There is, so far as I can see, no necessity 
for such an assumption, since there is present in every case a contin- 
uous medium of protoplasm, which would seem to make this idea at 
least superfluous. Moreover, the additional element that Driesch has 
added to his conception of the process, namely, an action in propor- 
tion to the size of the piece, is objectionable if for no other reason 
than that it attributes to the unknown principle of " action at a dis- 
tance" a quality that is the very thing that ought itself to be 
explained. This assumption, it seems to me, begs the entire ques- 
tion, and we can give no better explanation why it should belong to 
the principle of " action at a distance " than to anything else. Far 
from having given a demonstration of vitalism, Driesch has, I think, 
in his analysis simply set up an entirely imaginary principle, which, 
taken in connection with other undemonstrable qualities, is called 
vitalism. 

If we cannot accept Driesch's demonstration of vitalism, from 
what point of view can we deal with the phenomenon of the produc- 
tion of a typical form from each kind of living material.^ Can we 
find a physico-chemical explanation of the phenomenon } Enough 
has been said to show that this property is one of the fundamen- 
tal characteristics of living things and is, in all probability, a phe- 
nomenon which we certainly cannot at present hope to explain. 
Yet the question raised by Driesch is, at bottom, not so much 
whether we can give a physico-chemical explanation, but whether 
the phenomenon belongs to an entirely different class of phenom- 
ena from that considered by the physicist and by the chemist. Let 
us examine the results and see if we are really forced to conclude 
that there is no other physico-causal point of view possible. 

In many cases' in which a response to an external stimulus takes 
place, we must assume a physico-causal connection between the 
stimulus and the effect. The action of poisons, for instance, is an 

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286 REGENERATION 

example of this kind, and, in some cases, as in the formation of the 
galls of plants, the* stimulus of a foreign body may lead to the devel- 
opment of a structure, the gall, of a definite form. The experiments 
of Herbst on the effect of lithium salts in sea water on the develop- 
ment of the sea-urchin embryo lead to a similar conclusion. The 
changes in form that result from other external agents, such as light, 
gravity, contact, etc., can be best understood from a physico-causal 
point of view, and it seems improbable at least that their action 
within the organ is transformed into a vitalistic causal action through 
Driesch's principle of an ** action at a distance." ^ The effect of inter- 
nal factors on the change of form is, however, much more difficult 
to deal with, since we know so little at present about these factors. 
Here we find amongst other phenomena that of the proportionate 
formation of a whole organ from a part of an old one, or of an egg. 
We find it difficult, if not impossible, to attribute this directly to 
external causes, yet, as I have tried to show, the first steps through 
which, this takes place can be referred to physico-causal principles. 
These are the separation of the piece from the whole ; the change of 
the unsymmetrical piece into a symmetrical one, brought about, in part 
at least, by contractile phenomena in the piece, aided, no doubt, in some 
cases by surface tension, etc. These changes give the basis for the 
development of a new organization along the lines of structure that 
are already present in the piece. We find here the beginning of a 
physico-causal change, and, so far as I can see, we have no reason 
to suppose that at one stage in the process this passes over into the 
vitalistic-causal principle.- It should, I think, be pointed out in this 
connection that even in the physical sciences it would not be difficult 
to establish a vitalistic principle, or whatever else it might be called, 
if we chose to take into account such properties of bodies as those 
which the chemist calls the affinities of atoms and molecules, or the 
symmetrical deposition of material on the surface of a crystal from a 
supersaturated solution, etc. These phenomena are usually looked 
upon as " given," that is, beyond the hope of possible examination. 
Until these questions are more fully understood scientists are, I 
think, justified in showing a certain amount of self-restraint in regard 
to the solution of such problems. Du Bois-Reymond has summed 
up this point of view in the dictum, " Ignorabimus," which is inter- 
preted to mean, not only that we are ignorant at present on certain 
questions, but that we know we must remain ignorant. The forma- 
tive changes in the organism appear to belong to this category of ques- 
tions. This confession of ignorance need not mean that we cannot 
hope to discover the conditions under which the phenomena take place, 
so that we can predict with certainty what the results will be, but 

^ Not that Driesch supposes this would be the case. 

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GENERAL CONSIDERATIONS AND CONCLUSIONS 287 

the meaning of the change itself may remain forever obscure, at 
least from our present conception of physico-chemical principles. 
Shall we, therefore, call ourselves vitalists, because we find certain 
phenomena that we cannot hope to explain as the result of physical 
principles, or for which we must invent an unknown principle ? Or 
can we succeed in demonstrating a different kind of principle in liv- 
ing things ? If we could, we might be justified in calling ourselves by 
the name of vitalists. But who has made such a discovery ? Does 
the well-known phenomenon of proportionate development give a 
demonstration of the unknown principle? Would one be justified 
in claiming a different principle that is not a physico-causal one, 
because the nerve impulse is different from any known physical ph^e- 
nomenon ? The preceding pages have made clear, I hope, that/for 
my own part, I see no grounds for accepting a vitalistic principle 
that is not a physico-causal one, but perhaps a different one from 
any known at present to the physicist or chemist. ? 

In order to make clear in what way certain terms have been used 
in the preceding chapters, it may not be out of place to indicate how 
it is intended that they should be employed. The word " cause " has 
been used in the sense in which the physicist uses the term. A " stim- 
ulus" is the chain of effects of a cause acting on a living body. In cer- 
tain cases the cause itself may be spoken of as the stimulus, but 
only when its specific action on a living body is implied. A "factor" 
is a more general term and is usually one or more of a number of 
causes that produce a result. It may prove convenient to use this term 
where a change in form is produced. Thus the size of a piece is one 
of the factors that determines the result ; the part of the body from 
which the piece is taken may also be a factor, or rather the kind of 
material contained in the piece. These examples will suffice to show 
that the word is used for an observed connection of a very general 
sort, especially for those cases in which we have not analyzed the 
factor into its components. The term is especially useful for cases 
in which the change in form is the outcome of the innate properties 
of the organization. The term may be used so that it need not preju- 
dice the result, either in favor of a physico-causal or a vitalistic- 
causal point of view. It may be convenient to use it as an indifferent 
term in these respects. The word "force " I have attempted to avoid 
as far as possible, except in such current expressions as " the force of 
gravity," etc., for, apart from the loose way in which the word is used 
even by physicists, we know so little about the forces in the organ- 
ism that it is best, I think, to use the word as sparingly as possible, 
and only where a known physical force can be shown to produce an 
effect 



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288 REGENERATION 

Much misunderstanding has arisen in connection with the term 
" formative force.*' In the first place we naturally associate with this 
term the meanings attached to it by writers of the seventeenth and 
eighteenth centuries. They assumed a formative principle in living 
things, that is an expression of a formative force. Roux, who has 
more recently used the term, has attempted to avoid misunderstand- 
ing by using the plural, — **the formative forces of the organism"; 
but even under these circumstances, differences of opinion have 
arisen, as shown by the controversy between Roux ('97) and Hertwig 
('94 and *97), on this point. A change in form carries with it a 
change of position of the parts, and the latter involves the idea of 
forces, but the nature of these forces is entirely obscure to us, at 
least we cannot refer them to any better-known category of physical 
or chemical forces. They may, perhaps, be most profitably com- 
pared to the forces of chemical union, but whether they are very 
numerous or can be reduced to a limited number of^ kinds of force, 
we do not know. If it could be shown that the changes in the organ- 
ism are due to molecular changes, then the formative forces might 
appear to be only molecular forces, but we are not in position at 
present to demonstrate that this is the case, however probable it 
may appear. 

Finally, the use of the term " organization " may be considered, 
although from what has been said already it is clear that there must 
be sr certain amount of vagueness connected with our idea of what 
the organization can be. The organization, from the point of view 
that I have adopted, is a structure, or arrangement of the material 
basis of the organism, and to it are to be referred all the fundamental 
changes in form, and perhaps of function as well. We also use the 
term as applied to the completed structure, by which we mean that 
the organism consists of typical parts having a characteristic arrange- 
ment carrying out definite functions. When applied to the egg, 
or to a regenerating piece, the term refers to some more subtle struc- 
ture that we are led to suppose to be present from the mode of be- 
havior of the substance. As pointed out, we know this organization 
at present from only a few attributes that we ascribe to it, and are not 
in a position even to picture to ourselves the arrangement that we 
suppose to exist. 

REGENERATION AND ADAPTATION 

One of the most difficult questions with which the biologist has 
to deal is the meaning of the adaptation of organisms to their environ- 
ment. Pfluger, in an article entitled " The Teleological Mechanics of 
Living Nature," has drawn attention to the teleological character, or 
purposef ulness, of certain processes in the living organism. *' There 



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GENERAL CONSIDERATIONS AND CONCLUSIONS 289 

has been found only one general point of view, which if not absolute, 
yet is the rule, to account for the eternal transformations of energy in 
the living body. Only those combinations of causes take place that 
are as favorable as possible for the welfare of the animal. This holds 
true even when entirely new conditions are artificially introduced 
into the living organism. What is more remarkable than that, even 
in the highly organized mammal, there should be a regeneration of 
the bile duct after its removal, or that after a large piece of a nerve 
has been extirpated by a severe operation it should be again renewed.^ 
. . . What is more surprising than that the organism should become 
accustomed to the most diverse kinds of organic and inorganic poi- 
sons.** . , . And, finally, there are a number of facts that make good 
the law that changes appear to be governed by no other principle 
than the purpose of making certain the existence of the organism." 

Pfluger's teleological law of causality is that " the cause of every 
need of a living being is at the same time the cause of the fulfilment 
of the need." Pfliiger explains that the word "cause" is here intention- 
ally chosen in order to bring out the necessary, lawful connection in 
which the cause of each need stands in relation to the fulfilment of 
that need. He adds that it would have been more correct, but less 
pointed, to have said "motive" or "inducement" instead of "cause." 

In order to illustrate what is meant by this law, the following 
examples may be given. Food and water bring back the organism 
to its normal condition. The absence of food in the body leads to 
hunger, and this to the taking in of more food ; or, in other words, the 
need of food leads to the search for food, or at least to the taking in 
of food. The sexual desire, or the need to reproduce, brings about 
the condition of the animal that leads to reproduction. A defect in 
the valves of the heart leads to the enlargement of the right or the 
left ventricle. The removal of one kidney leads to the hypertrophy 
and increased function of the other. And although not explicitly 
stated by Pfliiger in this place, we may add to this list the removal 
of a part of an animal, that leads to the regeneration of that part. 
Pfliiger further states that we are making no subtle distinction when 
we point out that these phenomena, if looked at from the point of 
view of purposeful acts, appear to have a teleological side. In reply 
to this it may be stated, however, that in certain cases of regenera- 
tion it can be shown that the result is entirely useless, or even injuri- 
ous to the organism ; hence the teleological nature of the process is 
entirely lost sight of, and we are the more ready to accept a simple 
causal explanation of the phenomena. The best example of this 
that I can give is the development of a tail at the anterior end of a 
posterior piece of an earthworm. This process is not an occasional 
one, but is constant. An example of an apparently useful result, so 

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290 REGENERATION 

far as the individuars well-being is concerned, but entirely useless from 
the point of view of the continuance of the species, is found in the 
development, in the earthworm, of a new head after the removal of 
the anterior end, including the reproductive region. New reproductive 
organs are not formed, and, although, in virtue of the regeneration of 
a new head, the individual is capable of carrying on its existence, yet 
the race of earthworms is not thereby benefited. The production of 
two tails in lizards, or of two or more lenses in the eyes of newts, are 
examples of the regeneration of superfluous structures. 

If, however, it is claimed that in the large majority of cases the 
process of regeneration is for the welfare of the individual, and for 
the race also, this must be admitted, and it is this fact which has made 
a deep impression on the minds of many biologists. 

From the causal point of view, we may look upon the formative 
changes as the necessary outcome of strictly causal principles, and 
we may suppose that they take place without respect to the final 
result. But the question before us is rather to explain, if possible, 
why the changes that take place are in so many cases useful ones. 
That they are not always useful must be admitted, that they sometimes 
are must be granted, and it is the latter alternative that has attracted 
special attention. Now it is undoubtedly the simplest solution to 
claim that the scientist has nothing to do with the adaptiveness of the 
response, that his whole problem lies in a study of the causal phe- 
nomena involved in each process, but it is unquestionably true that 
scientists have not been satisfied to confine their hypotheses to this 
side of the question. The widespread interest in the theory of natu- 
ral selection is, I think, due to the fact that it appears to offer an 
explanation of the formation of adaptive processes — not that it 
pretends to explain the origin of the adaptive structures or processes 
themselves, but that it seems to account for the adaptiveness of the 
fully formed product, i,e, the organism. For it will be seen that if 
only those forms (variations) survive that are yseful, and survive 
either because the environment selects them (and exterminates the 
others), or because new forms that arise find a new place in nature 
where they can remain in existence, then the adaptiveness of the 
form to its surroundings would seem to be accounted for. In this 
case we can see how the causal processes that take place in the organ- 
ism need have no causal connection with the environment, — except 
in the sense that the environment has acted as a selective agent, and 
appears, therefore, in the light of a teleological factor. But, as has 
been said before, the question is not so much that organisms are 
adapted, as that organisms respond adaptively to changes to which 
they can never have been subjected before. It is for the latter fact 
that a solution is to be sought. 



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GENERAL CONSIDERATIONS AND CONCLUSIONS 29 1 

In this whole question there is danger of extending our own expe- 
rience as agents in the constructing of products useful to ourselves, to 
the organic world, in attempting to account for the way in which the 
useful characters of organisms have arisen. We see a ship being 
built, and we know that when it is finished it will be useful. We 
explain its building by its future usefulness, — that is, we explain the. 
process as the result of human teleology. But have we any right to 
extend this' principle to the organic world, and infer that processes are 
there carried out because they will ultimately be useful to the individual * 
in which they take place } Unconsciously we have shifted our point of 
view. The ship does not build itself, and the final result of the build- 
ing is of no use to the ship. On the contrary, the organism does 
build itself and the result is useful only to itself. Unless we suppose 
that some external agent acting as we do ourselves directs the 
formative processes in animals and plants, we are not justified in 
extending our experience as directive agents to the construction of 
the organic world ; and if we are not justified in drawing such a con- 
clusion, since the organism by no means always responds adaptively, 
and in many cases very badly and incompletely, then, it seems to me, 
we must look for another point of view. 

In connection with his work on the regeneration of the eye of the 
salamander, Gustav Wolff ('93) has made some sweeping statements 
in regard to the phenomenon of adaptation. " Purposeful adaptation 
is that which makes the organism an organism. It is this adaptation 
that appears to us as the most characteristic property of all living 
things. We can think of no organism without this characteristic." 
In another place he states, "... we recognize that every explana- 
tion that presupposes the living being, every post-vital explanation of 
organic adaptation, presupposes in every case that which it attempts 
to explain ; we recognize that the explanation of adaptation must co- 
incide with the explanation of life itself." There is, perhaps, some 
truth in this statement, but, on the other hand, Wolff has, I think, 
shot somewhat over the mark. As Fischel (1900) has pointed out, 
the response is sometimes not adaptive, as when two lenses develop 
in the same eye in the salamander ; and, we may add, as when an an- 
tenna develops in certain Crustacea in place of an eye, or as when a 
tail develops instead of a head, or a head in place of a tail. In the 
light of these facts, it is, I think, going too far to assert that the power 
of living things to respond adaptively to changes in themselves or in 
their environment is synonymous with life itself. All that we can 
fairly claim is that in several cases living forms have been shown to 
be able to complete themselves^ and this may be interpreted as an adap- 
tive response. It would carry us far beyond the scope of the present 
volume to discuss the question of adaptation in general, and I think it 

Digitized by VjOOQIC 



292 REGENERATION 

highly probable that it will prove true that there are many kinds of 
adaptive responses that must be considered separately and each on its 
own merits. Let us, therefore, confine our concluding remarks en- 
tirely to regenerative changes which, after they have been completed, 
are for the good of the organisms. Our preceding discussion has led 
to the conclusion that the phenomena of regeneration are not pro- 
cesses that have been built up by the accumulation of small advances 
in a useful direction ; that they cannot be accounted for by the sur- 
vival of those forms in which the changes take place better than in 
their fellows, for it is often not a question of life and death whether 
or not the process takes place, or even a question of leaving more de- 
scendants. On the contrary, it seems highly probable that the regen- 
erative process is one of the fundamental attributes of living things, 
and that we can find no explanation of it as the outcome of the selec- 
tive agency of the environment. The phenomena of regeneration 
appear to belong to the general category of growth-phenomena, and 
as such are characteristic of organisms. Neither regeneration nor 
growth can be explained, so far as I can see, as the result of the use- 
fulness of these attributes to the bodies with which they are indisso- 
lubly associated. The fact that the process of regeneration is useful 
to the organism cannot be made to account for its existence in the 
organism. 



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LITERATURE 

Aldrovandns, Ulysses. 

1642. Historia Monstrorum. MDCXLII. Cap. VIII. 

1645. Patritii boloniensis de quadrupedibus digitatis oviparis. Lib. II. Boloniae, 
MDCXXXXV. 
Allman, J. A. 

'64. Report of the present State of our Knowledge of the Reproductive System in the 
Hydroida. Report of the 33d Meeting of the British Assoc, 1864. 
Andrews, E. A. 

'90. Autotomy in the Crab. The American Naturalist, XXIV, 1890. 
*9i. Report upon the Annelida Polychaeta of Beaufort, North Carolina. Proc. U. S. 
National Museum, XV, p. 286, 1891. 
Andrews, 6. F. 

'97. Some Spinning Activities of Protoplasm, etc. Jour. Morph., XII, 1897. 
Apostolides, N. Christo. 

'82. Anatomie et d^veloppement des Ophiures. Arch. Zool. Experim., X, 1882. 
Aristotle. 

Historia de animalibus, Julio Caesare, Scaligero interprete, cum ejusdem CommentariiSc 
Tolosae. MDCXIX, Lib. II, Cap. XX. 
Amonlt de Nobleyille et Saleme. 

1756. Suite de la mati^re medicale de Geoffroy, t. 12, MDCCLVI. 
Aschoif, L. 

'95* Regeneration und Hypertrophie. Ergebnisse d. allg. Path. Morph. und Physiol., 
1895. 
Balbiani, E. 6. 

'88. Recherches exp^rimentales sur la merotomie des infusoires cili6s. Recueil zool. de 

la Suisse, V, 1888. 
'91. Sur les regenerations successives du peristome, etc., chez les stentors, etc. Zool. 

Anz., 1 89 1. 
'91. Nouvelles recherches experimentales sur la m6rotomie des infusoires cilies. Arch, 
microgr., IV et V, 1891-93. 
Bardeen, C. R. 

'01. On the Physiology of the Planaria maculata, etc. Am. Jour. Physiol., V, 1901. 
Barfurth, D. 

'9i-'oo. Regeneration. Ergebnisse Anat. und Entwickl. Merkel und Bonnet, 1891- 

1900. 
'91. Versuche zur funktionellen Anpassung. — Zur Regeneration der Gewebe. Arch. 

f. Mikr. Anat, XXXVII, 1891. 
'93. Experimentelle Untersuchungen fiber die Regeneration der Keimblatter bei den 

Amphibien. Anat. Hefte, IX, 1893. 
'94. Die Experimentelle Regeneration uberschfissiger Gliedmassenteile bei den Amphi- 
bien. Arch. f. Entw.-mech., I, 1894. 
'99. Sind die Extremitaten der Frosche regenerationsfahig ? Arch. f. Entw.-mech., IX, 

1899. 
'99. Die Experimentelle Herstellung der Cauda bifida bei Amphibienlarven. Arch. f. 
Entw.-mech., IX, 1899. 

293 Digitized by CjOOQ IC 



294 REGENERATION 

Barroia, J. 

'77. Memoire lur I'embryologie dei n^mertes. Ann. Sc. Nat. (6), tome VI, 1877. 
Bateson, W. 

'94. Materials for the Study of Variation, 1894. 
Baudelot, E. 

'69. De la regeneration de Textremite c^phalique chez le Lombric terrestre. Boll. Soc 
d. Sc. Nat., Strassbourg, II, 1869. 
Benliam, W. B. 

'96. Fission in Nermertines. Q. J. Micr. Sc., XXXIX, 1896. , 

Bergh, R. 8. 

'96. Ober den BegrifF der Heteromorphose. Arch. f. Entw.-mech., Ill, 1896. 
Bert, P. 

'60. Recherches Experimentales. Ann. d. Sc. Natur. (5 Ser.), V, i86a 
Bickford, B. E. 

'94. Notes on Regeneration and Heteromorphosis in Tubularian Hydroids. Joum. 
Morph., IX, 1894. 
Blumenbach. 

1787. Specimen physiologiae comparatae inter animantia calidi et frigidi sanguinis; in 
commentationes soc. reg. scient. Gottingensis, Vol. VIII. Gottingae, 1787. 
Bock, M. yon. 

'97. tjber die Knospung von Chaetogaster diaphanus. Jena. Zeit f. Naturw., XXXI, 
1897. 
Bonnet, C 

1745. Traite d'insectologie. Seconde partie. Observations sur quelques esp^ces de vers 
d'eau douce, qui coupes par morceux, deviennent autant d'animaux complets. 
Paris, 1745. 
Bordage, B. 

'97. Phenom^nes d'autotomie observes chez les Nymphes de Monandroptera inuncans 
et de Kaphiderus scabrosus. Compt. Rend, des seances de la Soc. de Biologie. Paris, 

1897. 
'97. Sur la regeneration tetramerique du tarse des Phasmides. Ibid,^ 1897. 
'98. Sur les localisation des surfaces de regeneration chez les Phasmids. Ibid,^ 1898. 
'98. Gas de regeneration du bee des oiseaux explique par la loi de Lessona. Ibid,^ 

1898. 
'99. Regeneration des membres chez les Mantides, etc. Ibid,., XXVIII, 1899. 
'99. Sur le mode probable de formation de la soudure-femoro-trochanterique chez les 

Arthropodes. Ibid., XXVIII, 1899. 
'00. On the Absence of Regeneration in the Posterior Limbs of the Orthoptera Salta- 

toria and its Probable Gauses. Ann. and Mag. of Nat. Hist., 1900. 
'00. Regeneration of the Tarsus and of the Two Anterior Parts of Limbs in the Orthop- 
tera Saltatoria. Ibid,, 1900. 
Bom, 6. 

'97. Uber Verwachsungsversuche mit Amphibienlarven. Arch. f. Entw.-mech., IV, 1897. 
Boulenger, 6. A. 

'88. On the Scaling of the Reproduced Tail in Lizards. Proc. Zool. Soc, London, 1898. 
Boveri, Th. 

'89. Ein geschlechtlich erzeugter Organ ism us ohne miitterliche Eigenschaflen. Sitz- 

ungsber. Ges. Morph. Phys. Miinchen, V, 1889. 
'95. Uber die Befruchtungs- und Entwickelungsfahigkeit kernloser Seeigeleier. Arch. f. 

Entw.-mech., II, 1895. 
*oi. Uber die Polaritat des Seeigel-Eies. Verhand. d. Phys.-Med. Gesell. Wiirzburg 

(N. F.), XXXIV, 1901. 
Brand, F. 

'96. Fortpflanzung und Regeneration von Lemanea fluviatilis. Berichte d. deutsch. 

botan. Gesell., V, 1896. 

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LITERATURE 295 

Brefeld, 0. 

'77. Die Entwickelungsgeschichte der Basidiomyceten. Botan. Zeit., 1876. 
'77. Botanische Untersuchungen. Schimmelpilze, III (page 69), 1877. 
Brindley, H. H. 

'97. On the Regeneration of Legs in the Blattidae. Proc. 2k)ol. Soc., London, 1897. 
'98. On certain Characters of Reproduced Appendages in Arthropoda, particularly in the 
Blattidae. lind., 1898. 
Broossonet, M. 

1 786. Observations sur la regeneration de quelques parties du corps des Poissons. Hist, 
d. I'Acad. Roy. des Sciences, 1786. 
BiUow, C. 

*82. (Jber Theilungs- iind Regenerations- vorgange bei Wurmem. Arch. Naturg., XLIX, 

1882. 
'83. Die Keimschichten des wachsenden Schwanzendes von Lumbriculusvariegatus, etc. 

Zeit. Wiss. Zool.. XXXIX, 1883. 
'83. (jber anscheinend freiwillige und kunstliche Theilung mit wechselnder Regenera- 
tion bei Coelenteraten, Echinodermen, und Vermes. Biol. Centralbl., Ill, 1883-84. 
Byrnes, Esther F. 

'98. On the Regeneration of Limbs in Frogs after the Extirpation of Limb Rudiments. 
Anat. Anz., XV, 1898. 
Cadiat, 0. 

'76. Du cristallin, anatomie et developpement, usage et regeneration. Th^ d'agr^ga- 
tion. Paris, 1876. 
Cardanus, Hieronymus. 

1580. Mediolanensis, medici, de subtilitate. Lugundi, MDLXXX. 
Camot, P. 

*99. Les regenerations d'organs. Paris, 1899. 
Carriere, J. 

'80. Studien fiber die Regenerations-Erscheinungen bei den Wirbellosen. Wiirzburg, 
1880. 
Chabry, L. 

'87. Contribution ^ Tembryologie normale et teratologique des ascidies simples. Journ. 
Anat. et Phys., XXIII, 1887. 
Chantran, 8. 

'73. Experiences sur la regeneration des yeux chez les ecrevisses. Compt. rend., LXXVI, 

1873. 
Chun, C. 

'92. Die Dissogonie der Rippenquallen. Festschr. f. Leuckart, 1892. 
Colucci, V. 8. 

'85. Studio sperimentale sulla rigenerazione degli arti e della coda nei Tritoni. Rende- 

conto delle sessioni della R. Accad. d. Scienze dell' 1st. di Bologna, 1885. 
'91. Sulla regenerazione parziale delP occhio nei Tritoni. Memorie della R. Accad. 
delle Scienze dell' 1st. di Bologna (Ser. V), I, 1891. 
Conklin, E. 6. 

'98. Environmental and Sexual Dimorphism in Crepidula. Proc. Acad. Nat. Science, 
Philadelphia, 1898. 
Contijan. 

'90. Sur Tautotomie chez la Sauterelle et le Lezard. Compt. rend., 1890. 
Coutidre, H. 

'98. Notes sur quelques cas de regeneration hypotypique chez Alpheus. Bull. Soc. Ent., 
France, 1898. 
Crampton, H. E. 

'96. Experimental Studies on Gasteropod Development. Arch. f. Entw.-mech., Ill, 

1896. 
'97. The Ascidian Half-Embryo. New York Acad, of Sc., X, 1897. ^-^ 

Digitized by LjOOQIC 



296 REGENERATION 

Dalyell, J. G. 

'14. Observations on Some Interesting Phenomena in Animal Physiology, exhibited 

by Several Species of Planariae. Edinburgh, 18 14. 
'47. Rare and Remarkable Animals in Scotland. London, 1847-48. 
'5 1 . Powers of the Creator, 1 85 1 . 

Darwin, C. 

'54. Monograph of the Cirrepedia, 1854. 

'68. The Variation of Animals and Plants under Domestication, 1868. 

Davenport, C. B. 

'93. Studies in Morphogenesis. I. On the Development of the Cerata in Aeolis. Bull. 

Mus. Comp. Zool., XXIV, 1893. 
'94. Studies in Morphogenesis. Nr. 2. Regeneration in Obelia and its Bearing on 

Differentiation in the Germ-plasma. Anat. Anz. 9, 1894. 
*97. Experimental Morphology, I and II. New York, 1897-99. 

Dawydoff, C. 

'01. Beitrage zur Kenntnis der Regenerations Erscheinungen bei den Ophiuren. Zeit. 
Wiss. Zool., LXIX, 1901. 
Delage, Y. 

*95. La Structure de Protoplasma et les Theories sur L'Her6dite, 1895. 

'99. £ltudes sur la Merogonie. Arch. de'Zool. experim. et generale, 1899. 

Dendy, A. 

'56. On the Regeneration of the Visceral Mass in Antedon Rosaceus. Stud. Biol. Lab., 
Owens College, I, 1856. 

Dewitz, H. 

'94. ijber das Abwerfen der Scheeren des Flusskrebses. Biol. Centralb., V, 1894. 

Driesch, H. 

'90. Heliotropismus bei Hydroidpolypen. 2^ol. Jahrb. (Syst. Abt.), V, 1890. 

'91. Die Stockbildung bei den Hydroidpolypen und ihre theoretische Bedeutung. Biol. 

Cent.. XI, 1891. 
'91. Die mathematisch-mechanische Betrachtung morphologischer Probleme der Biolo- 

gie. Jena, 189 1. 
*9i-'93. Entwickelungsmechanische Studien. 
'91. I. Der Wert der beiden ersten Furchungszellen in der Echinodermenentwick- 

elung. Zeit. f. wiss. Zool., LIII, 1 891. 
'91. II. Ober die Beziehungen des Licbtes zur ersten Etappe der tierischen Formbildung. 

Ibid. 
'92. III. Die Verminderung des Furchungsmaterials und ihre Folgen. Zeit. f. wiss. 

Zool., LV, 1892. 
'92. IV. Experimentelle Veranderungen des Typus der Furchung und ihre Folgen. 

Ibid. 
'92. V. Von der Furchung doppelbefurchteter Eier. Ibid, 
'92. VI. Uber einige allgemeine Fragen der theoretischen Morphologie. Ibid. 
*93. VII. Exogastrula und Anenteria. Mitt. zool. Stat. Neapel, II, 1893. 
'93. VIII. Uber Variation der Micromerenbildung. Ibid. 

'93. IX. .pber die Vertretbarkeit der " Anlagen** von Ektoderm und Entoderm. Ibid, 
*93. X. Uber einige allgemeine entwicklungsmechanische Ergebnisse. Ibid. 
*92. Kritische Erorterungen neuerer Beitrage zur theoretischen Morphologie. II. Zur 

Heteromorphose der Hydroidpolypen. Biol. Cent., XII, 1892. 
'93. Zur Verlagerung der Blastomeren des Echinideneies. Anat. Anz., VIII, 1893. 
•93. Zur Theorie der tierischen Formbildung. Biol. Cent., XIII, 1893. 
'93. Die Biologic als selbstandige Grundwissenschaft. Leipzig, 1893. 
*94. Analytische Theorie der organischen Entwickelung. Leipzig, 1894. (Also Arch. 

f. Entw.-mech., IV, 1896.) 
*95. Von der Entwickelung einzelner Ascidienblastomeren. Arch. f. Entw.-mech., I, 

1895. 

Digitized by LjOOQIC 



LITERATURE 297 

•95. Zur Analysis der Potenzen embryonaler Organzellen. Arch. f. Entw.-mech., II, 

1895. 
'96. Die Maschinentheorie des Lebens. Biol. Cent., XVI, 1896. 
'96. Uber den Anteil zufalliger individueller Verschiedenheiten an ontogenetischen 

Versuchsresultaten. Arch. f. Entw.-mech., Ill, 1896. 
'96. Die taktische Reizbarkeit der Mesenchymzellen von Echinus microtuberculatus. 

Arch. f. Entw.-mech., Ill, 1896. 
'96. Betrachtungen iiber die Organisation des Eies und ihre Genese. Arch. f. Entw.- 
mech., IV, 1896. 
'96. Uber einige primSlre und sekundare Regulationen in der Entwickelung der Echino- 

dermen. Arch. f. Entw.-mech., IV, 1896. 
'96. Zur Analyse der Reparationsbedingungen bei Tubularia. Vicrteljahrsschr. Nat. 

Ges., Zurich, XVI, 1896. 
'97. Uber den Wert des biologischen Experiments. Arch. f. Entw.-mech., V, 1897. 
'97. Neuere Beitrage zur exakten Morphologic in englischer Sprache. Ill (1896). 

Arch. f. Entw.-mech., V, 1897. 
'97. Studien iiber das Regulatiunsvermogen der Organismen. I. Von den Regulationen 

Wachstums- und Diflfereuzierungsfahigkeiten der Tubularia. Arch. f. Entw.-mech., 

V, 1897. 
'97. Von der Beendigung morphogener Elementarprozesse. Arch. f. Entw.-mech., V, 

1897. 
'98. Uber rein mutterliche Charactere an Bastardlarven von Echiniden. Arch. f. Entw.- 
mech., VII, 1898. 
'99. Von der Methodc der Morphologie. Biol. Cent., XIX, 1899. 
'99. Die Lokalisation morphogenetischer Vorg&nge. Ein Beweis vitalistischen Ge- 

schehens. Arch. f. Entw.-mech., VIII, 1899. 
'99. Studien uber das Regulationsverm5gen. II. Quantitative Regulationen bei der 

Reparation der Tubularia. Arch. f. Entw.-mech., IX, 1899. III. Notizen iiber die 

AuHosung und Wiederbildung des Skeletts von Echinidenlarven. Ibid, 
'cx3. Die isolirten Blastomeren des Echinidenkeimes. Arch. f. Entw.-mech., X, 

1900. 
*oo. Studien uber das Regulationsvermogen der Organismen. IV. Die Verschmelzung 

der IndividualitSt bei Echinidenkeimen. Arch. f. Entw.-mech., X, I9cx>. 
'99. Resultate und Probleme der Entwickelungsphysiologie der Thiere. Ergebn. d. 

Anat. u. Entw. (1898), 1899. 
01. Studien iiber das RegulationsvermSgen der Organismen. V. Erganzende Beob- 

achtungen an Tubularia. Arch. f. Entw.-mech., XI, 1 901. 

Driesch, H. and Morgan, T. H. 

'95. Zur Analysis der ersten Entwickelungsstadien des Ctenophoreneies. Arch. f. Entw.- 
mech., II, 1895. (Also Driesch : Bemerkungen, etc., Zool. Anz., 1896.) 

Dugds, A. 

'28. Recherches sur la circulation, la respiration et la reproduction des Annelides 

abranches. Annales des Sci. nat. (5), XVI, 1828. 
'29. Memoire sur les esp^ces indigenes du genre Lacerta. Annales des Sciences natu- 

relles, XVI, 1829. 
Dum^ril, A. 

'67. Experiences d^montrant que la vie aquatique des Axolotle abranchies exterieurs 

se continue apr^s Tablation des louppcs branchiales. Nouvelles Archives du Museum. 

Ill, 1867. 

Dnyne, J. van. 

'96. ijber Heteromorphose bei Planarien. Pfluger*s Arch., LXIV, 1896. 

Ehlers, E. 

'69. Die Neubildung des Kopfes und der vorderen Korpertheile bei polychaeten Anne- 

liden. Erlangen, 1869. 
'99. Palolo. Biol. Centralb., XIX, 1899. 



Digitized by LjOOQIC 



298 REGENERATION 

Eimer, Th. 

'73. Ober Kfinstliche Theilbarkeit von Aurelia aurita und Cyanta capiUata, Verli« 
d. phys..mcd. GescU. zu Wurzburg (N. F.), VI (Dec), i873- 
Emery, C. 

'97. Wer hat die Regeneration der Augenlinse aos dem Irisepithel zuerst erkannt und 
dagestellt ? Anat. Anz., XIII, 1897. 
Endros, H. 

'95. Anstichversuche an Eiern von Rana fusca. II. TheiL Arch. f. Entw.-mech., II, 

1895-96. 
'95. Uber Anstich- und Schnfirversuche an Eier von Triton taeniatus. 73 Jahreb. d. 
Schlea. Ges. f. Vaterl. Kultur, 18 Juli, 1895. 
Endres, H., and Walter, H. E. 

'95. Anstichversuche an Eiern von Rana fusca. I. Theil. Arch. f. Entw.-mech., II, 
1895. 
Fiedler, K. 

'91. Entwickelungsmechanische Studien an Echinodermeiem. Festschr. Nageli u. 
K6lliker, Zurich, 1891. 
Fischel, A. 

'97. Experimentelle Untersuchungen am Ctenophorenei, 1-4. Arch. f. Entw.-mech., VI, 

1897-98. 
'98. Uber die Regeneration der Linse. Anat Anz., XIV, 1898. 
Flemmln^, W. 

'80. tJber Epithelregeneration und sogen. freie Kernbildung. Arch. f. mikr. Anat., 
XVIII, 1880. 
Flezner, S. 
. / '98. The Regeneration of the Nervous System of Planaria torva and the Anatomy of the 
^ Nervous System of Double-headed Forms. Jour. Morph., XIV, 1898. 

Forest-Heald, F. de. 

'98. A Study of Regeneration as exhibited by Mosses. Bot. Gaz., XXVI, 1898. 
Fraisse, P. 

'85. Die Regeneration von Geweben und Organen bei den Wirbelthieren, besonders 
bei Amphibien und Reptilien. Kassel und Berlin, 1885. 
Fredericq, L. 

'83. Sur Vautotomie ou mutilation par voie reflexe comme moyen de defense chez les 

animaux. Arch. d. Zool. experim. (Ser. i), 1883. 
'87. L'autotomie chez les etoiles de mer. Revue ScientiHque (Ser. 3), XIII, 1887. 
'93. L'autotomie ou la mutilation dans le r^gne animal. Bull, de TAcad. roy. de Bel- 
gique (Ser. 3), XXVI, 1893. 
Frenzel, J. 

*9i. Uber die Selbstverstummelung (Autotomie) der Thiere. Arch. f. d. Ges. Fhysiol., 
L, 1891. 
Friedlander, B. 
^ '95. Ober die Regeneration herausgeschnittener Theile des Central nerven-systems von 
Regenwiirmem. Zeit f. Wiss. Zool. LX, 1895. 
'98. Uber den sogennanten Palolo-^mrm. Biol. Cent., XVIII, 1898. 
»99. Nochmals der Palolo, etc. Biol. Centralbl., XIX, 1899. 
Fuhrmann, M. 

'98. Sur les phenom^nes de la regeneration chez les Invert^bres. Arch. Sc. Nat., V, 
1898. 
Cachet, M. H. 

'34. M^moire sur la reproduction de la queue des reptiles sauriens. Actes de la soci^te 
linneenne de Bordeaux, Nr. 36, 25 Juillet, 1834. 
Gayat, M. J. 

'73. Experimentalstudien iiber Linsenregeneration. Klin. Monatsbl. fiir Augenheilk., 
1873. 



Digitized by LjOOQIC 



LITERATURE 299 

Gesner, Conrad. 

1686. HUtoriae animalium. Lib. II, MDCLXXXVI. 
Giard, A. 

*95. Polydactylic provoqu6c chez Plearodeles Walthii Mich. Compt. Rend. Soc. BioL, 

II, 1895. 
'96. Y a-t-il antagonisme entre la " Greflfe " et la " Regeneration." Ibid,^ 1896. 
*97. Sur les regenerations hypotypiques. Ibid.y IV, 1897. 
'97. Sur I'autotomie parasitaire, etc. IbicL^ 1^97* 
Gluckselig, M. Ch. 

'63. Uber das Leben der Eidechsen, Vcrhandl. d. zool.-bot. Vereins in Wien., XIII, 1863. 
Godelmann, R. 

'01. Beitrage zur Kenntniss von Bacillus Rosii Fabr. mit besonderer Beruchsichtigung 
der bei ihm vorkommenden Autotomie und Regeneration einzelner Gliedmassen. 
Arch. f. Entw.-mech., XII, 1901. 
Goebel, K. 

'98. Organographie der Pflanzen. I. Allgemeine Organographie, Jena, 1898. 
Goette, A. 

'69. Uber Entwickelung und Regeneration des Gliedmassenskeletts der Molche. Tu- 
bingen, 1869. 
Gonin, J. 

'96. £tude sur la Regeneration du cristallin. Ziegler's Beitrslge z. pathol. Anat., XIX, 
1896. 
Goodsir, H. D. S. 

'44. A Short Account of the Mode of Reproduction of Lost Parts in the Crustacea. 
Ann. and Mag. Nat. Hist., XIII, 1844. 
Graber, V. 

'67. Zur Entwickelungsgeschichte und ReproductionsfSbigkeit der Othopteren. Be- 
richte d. kaiserl. Akad. d. wiss. Wien. LV, 1867. 
Greef, R. 

'67. Uber Actinosphaerium Eichhornii, etc. Arch. f. Mikr. Anat., Ill, 1867. 
Griffini e Marchio. 

*99. Sulla rigenerazione totale della retina nei tritoni. Riforma med., 1899. 
'99. Sur la regeneration de la ratine chez les tritons. Arch. ital. de Biolog., XII. 
Gniber, A. 

'84-'s. Uber Kunstliche Theilung bei Infusorien, L Biolog. Centralbl., IV, 1884-85. 

'85-'6. Same, Part II. IHd,, V, 1885-86. 

'86. Beitrage zur Kenntniss der Physiologic und Biologie der Protozoen. Ber. Nat. Ges. 

Freiburg, I, 1886. 
'87. Mikroskopische Vivisektion. Ber. d. Naturfor. Gesell. zu Freiburg, II, 1887. 

Haeckel, E. 

'68. Monographic der Moneren. Jena Zeit. f. Naturwiss., IV, 1868. 
'69. Entwickelungsgeschichte der Siphonophoren (page 73), 1869. 
'78. Die Kometenform der Seesterne und der Generationswechsel der Echinodermen. 
Zeit. f. wiss. Zool., XXX, 1878. 

Hargitt, C. W. 

'97. Recent Experiments on Regeneration. Zool. Bull., I, 1897. 

*99. Experimental Studies upon Hydromedusae. Biolog. Bull., I, 1899. 
Harrison, R. G. 

'98. The Growth and Regeneration of the Tail of the Frog Larva. Arch. f. Entw.- 
mech., VII, 1898. 
Hasse, H. 

'98. Uber Regeneration bei Tubifex rivulorum. Zeit. wiss. Zool., LXV, 1898. 
Hazen, A. P. 

'99. The Regeneration of a Head instead of a Tail in an Earthworm. Anat. Anz., 
XVI, 1899. 



Digitized by LjOOQIC 



300 REGENERATION 

Heider, K. 

'97. 1st die KeimbUtterlehre erschuttert? Zool. Centralb., IV, 1S97. 
Heineken, C. 

'28-' 29. Experiments and Observations on the Casting off and Reproduction of the Legs 
in Crabs and Spiders. The Zool. Journal, IV, 1828-29. 
Hepke, P. 

'97. tJber histo- und organogenetische Vorgange bei den Regenerationsprozessen der 
Naiden. Zeit. wiss. Zool., LXV, 1897. 
Herbst, C. 

'94. Uber die Bedeutung der ReizphN'siologie fur die kausale Auffassung von Vorgangen 

in der tierischen Morphalogie. Biol. Centralb., XIV und XV, 1894 u. 1895. 
'95-'99' Ober die Regeneration antennenahnlicher Organe an Stelle von Augen I. 

Arch. f. Entw.-mech., II, 1895. 
*96. II. Versuche an Sicyonia sculpta. Vierteljahrsschr. d. Naturf.-Ges., Zurich, 1896. 
'99. Ill u. IV. Weitere Versuche, u. s. w. Arch. f. Entw.-mech., IX, 1899, 
'96. Experimentelle Untersuchungen fiber den Einfluss der veranderten chemischen 

Zusammensetzung, etc. Arch. Entw.-mech., II, 1896. 
'97. Uber die zur Entwickelung der Seeigellarven nothwendigen anorganischen Stoff, 
I. Ibid,, V, 1897. 
Herciilais, K. d'. 

'75. Recherches zur Torganisation et la developpement des volucelles, 1875. 
Herlitzka, A. 

'96. Contributo alio studio della capacita evolutiva dei due primi blastomeri nell' uovo 
di tritoni (triton cristatus). Arch. f. Entw.-mech., II, 1896. ' 

Herrick, F. H. 

*95. The American Lobster. Bull. U. S. Fish Commission, 1895. 
Hertwig, 0. 

'85. Das Problem der Befruchtung und der Isotropic des Eies. Jena Zeit., XVIII, 1885. 
*85. Welchen Einfluss iibt die Schwerkraft auf die Teilungen der 2^llen? Ibid,, 1885. 
'90. Experimentelle Studien am tierischen £i vor, wahrend und nach der Befruchtung. 

Ibid., XXIV, 1890. 
'92. Urmund und Spina bifida. Arch. f. mikr. Anat. XXXIX, 1892. 
*92. Altere und neuere Entwickelungstheorien. Rede. Berlin, 1892. 
'93. Uber der Wert der ersten Furchungszellen f^r die Organbildung des Embryo. 

Arch. f. mikr. Anat. XLII, 1893. 
*94. Zeit- und Streitfragen der Biologic, I. Praformation oder Epigenesis? Jena, 1894. 
'95. Beitrage zur experimentellen Morphologic und Entwickelungsgeschichte. I. Die 
Entwickelung des Froscheies unter dem Einfluss schwacherer und starkerer Kochsalz- 
losungen. Arch. f. mikr. Anat., XLIV, 1895. 
*96. Experimentelle Erzeugung tierischer Missbildung. Festschr. Gegenbaur., II, 1896. 
'97. Zeit- und Streitfragen, II. Mechanik und Biologic, Jena, 1897. 
'98. Uber den Einfluss der Temperature auf die Entwickelung von Rana fusca und 

Rana esculenta. Arch. f. mikr. Anat, LI, 1898. 
'98. Die Zelle und Die Gewebe. II. Allgemeine Anatomic und Physiologic der 

Gewebe. Jena, 1898. 
'98. Beitrage, etc., IV. Uber einige durch Centrifugalkraf^ in der Entwickelung des 
Froscheies hervorgerufene Veranderungen. Arch. f. mikr. Anat, LI II, 1898. 
Hescheler, K. 

'96-'98. Uber Regenerationvorgange bei Lumbriciden, I u. II. Jena. Zeit., XXX, 1896, 
und XXXI, 1898. 
Hirota, S. 

'95. Anatomical Notes on the "Comet" of Linkia Multifora. Zool. Mag. Tokyo, 
VII, 1895. 
His, W. 

'75. Unsere Korperform und das physiologische Problem ihrer Entstehung. Leipsig, 
1875. 

Digitized by LjOOQIC 



LITERATURE 3OI 

Hofer, B. 

'89. Experimentelle Untersachungen uber den Einfluss des Kems auf das Proto- 
plasma. Jena. Zeitsch. f. Naturf. (N. F.), XVII, 1889. 
Horst, R. 

'86. Zur Regenerationslitteratur. Zool. Anz., IX, 1886. 

Boy, P. R. 

'71. The Development of Amblystoma lurida. The American Naturalist, 1871. 
Bubrecht, A. A. W. 

'87. Report on the Nemertines. Reports of the Challenger Expedition, 1887. 
Ischikawa, C. 

'90. Trembley's Umkehrungsversuche an Hydra nach neuen Versuchen erklart Zeit. 
f. wiss. Zool., XLIX, 1890. 
Joest, E. 

'95. Transplantationsversuche an Regenwurmern. Sitz. ber. d. Gesell. z. Berf. d. ges. 

Naturwiss. zu Marburg, 1895. 
'97. I'ransplaiitationsversuche an Lumbriciden. Arch. f. Entw.-mech. V, 1897. 
Johnstonus, Joannes. 

1657. Historiae naturalis de quadrupedibus. Amstelodami, MDCLVII, 1. 1, lib. IV, c. 
II, art. I u. art. II. 
Kennel, J. von. 

'82. tjber Teilung und Knospung der Tiere. Dorpat, 1882. 
'82. Ober Ctenodrilus pardalis. Arb. a. d. zool. zoot. Inst. Wdrzburg, V, 1882. 
'88. Biologische und Faunistische Notizen aus Trinidad. Arb. d. Zool.-Zoot Inst., 
Wurzburg, VI, 1888. 

Kinberg, J. 6. H. 

'67. . Om regeneration af hufvudet och de fr&mre segment ema hosen Annulat. Oefversigt 
af. kongl. Vetenskaps Akadamiens Forhandlmgar, 1867. 
King, H. D. 

'98. Regeneration in Asterias vulgaris Arch. f. Entw.-mech., VII, 1898. 
'00. Further Studies on Regeneration in Asterias vulgaris. Ibid.^ IX, 1900. 
Klein, Edm. J. 

'95-*97. Regeneration, Transplantation und Autotomie im Thierreich. Fauna Luxem- 
burg, 5-7. 1895-97. 
Knight, T. A. 

'09. On the Origin and Formation of Roots. Phil. Trans., 1809. 
Kny, L. 

'89. Umkehrversuch mit Ampelopsis quinquefolia. Berichte d. deutsch. botan. 
Gesellsch., VII, 1889. 
Kochs, W. 

'97. Versuche uber Regeneration von Organen bei Amphibien. Arch. f. mikr. Anat., 
XLIX, 1897. 
Korschelt, E. 

'97. Uber das Regenerationsverm5gen der Regenwfirmer. Sitzungsber. Ges. Naturw., 

Marburg, 1897. 
'98. Uber Regenerations- und Transplantationsversuche bei Lumbriciden. Ber. Zool. 
Ges., 1898. 
Kowaleyski, A. F. 

'72. liber die Vermehrung der Seesteme durch Theilung und Knospung. Zeit. wiss. 
Zool., XXII, 1872. 
Kramer, A. 

*47. Uber den Palolowurm, 1847. 

'99. Palolo untersuchungen. Biol. Centralbl., XIX, 1899. 

'99. Palolo untersuchungen in October und November, 1898. IHcU 

Digitized by LjOOQIC 



302 REGENERATION 

KrAass, H. 

'98. Selbstverstiimmelungen bei den Heuschrecken. Prometheus, IX, 1S98. 
Kioeber, J. 

*oo. An Experimental Demonstration of the Regeneration of the Pharynx of Allolo* 
bophora from Endoderm. Biol. Bulletin, II, 1900. 
Lac^p^de, B. 6. E. de. 

1788. Histoire naturelle des quadr. ovip. et des serpentes. 1788. 
Lang, A. 

'88. Uber den Einfloss der festsitzenden Lebensweise auf die Thiere. Jena, 1888. 
LefdYre, 6. 

'98. Regeneration in Cordylophora. Johns Hopkins University Circulars, Feb. 8, 1898. 
Lessona, M. 

'69. Sulla reproduzione della parte in multi animali. Atti della Soc. Ital., X, 1869. 
Lillie, F. R. 

'96. On the Smallest Parts of Stentor capable of Regeneration. Joum. Morph., XII,. 
1896. 
Lillie, F. R., and Knowlton, F. P. 

'97. On the Effect of Temperature on the Development of Animals. ZooL Bulletin,. 
I, 1897. 
Lindemuth, H. 

Ober Bildung von Bulben, etc. Ber. bot. Gesell., XIV. 
Loeb, J. 

'91. Untersuchungen zur physiologischen Morphologie derTiere. I. XJber Heteromor- 

phose. Wiirzburg, 1891. 
*92. Untersuch., etc. II. Organbildung und Wachstum. Wiirzburg, 1892. 
'92. Investigations in Physiological Morphology. III. Experiments on Cleavage. Joum* 

Morph., VII, 1892. 
*94. On Some Facts and Principles of Physiological Morphology. Biol. Lect., Woods 

Holl, in 1893, 1894. 
'94. Uber eine einfache Methode, zwei oder mehr zusammengewachsene Embryonen ana. 

einem Ei hervorzubringen. Pfluger's Arch., LV, 1894. 
*94. Uber die Grenzen der Teilbarkeit der Eisubstanz. Pfluger*s Arch., LIX, 1894- 
'95. Beitrage zur Entwickelungmechanik der aus einem Ei entstehenden Doppelbild- 

ungen. Arch. f. Entw.-mech., I, 1895. 
'95. ^emerkungen uber Regeneration. Arch. f. Entw.-mech., II, 1895. 
'96. Uber den Einfiuss des Lichts auf Organbildung bei Tieren. Pfliiger*s Arch., LXIII,. 
1896. 
\j '96. Hat das Centralnervensystem einen Einfiuss auf die Vorgange der Larvenmeta- 
morphose ? Arch. f. Entw.-mech., IV, 1896. 
*97. Zur Theorie der physiologischen Licht- und Schwerkraflwirkungen. Pfluger*s Arch.» 

LXVI, 1897. 
'98. On Egg-Structure and the Heredity of Instincts. Monist., VIII, 1898. 
'98. Assimilation and Heredity. Monist., VIII, 1898. 
'99. Uber die angebliche gegenseitige Beeinflussung der Furchungzellen und die Entste- 

hung der Blastula. Arch. f. Entw.-mech., VIII, 1899. 
*99. Warum ist die Regeneration kernloser ProtoplasmastUcke unmdglich oder erschwert? 

Arch. f. Entw.-mech., VIII, 1899. 
*oo. On the Transformation and Regeneration of Organs. Am. Joum. of PhysioL, 
IV, 19CX). 
Loeb, L. .. 

*97. Uber Transplantation von Weisser Haut auf einen Defect in Schwarzer Haut nnd 
umgekehrt am Ohr des Meerschweinchens. Arch. f. Entw.-mech., VI, 1897. 
'98. Ober Regeneration des Epithels. Arch, f. Entw.-mech., VI, 1898. 
*99. An Experiment-Study of Transformation of Epithelium to Connective Tissue. 
Medicin, 1899. 



Digitized by LjOOQIC 



LITERATURE 303 

Mcintosh, W. C. 

'70. Notes on the Development of Lost Parts in the Nemerteans. Journ. Linn. Soc., X, 

1870. 
*73-'74. Marine British Annelids. 1873-74. 
Magnus, Albertus. 

1661. Ordinis praedicatorum de animalibus. Lib. XXVI, tome VI. Lugundi, MDCLI. 
Mall, F. P. 

'96. Reversal of the Intestine. Johns Hopkins Hospital Reports, I, 1896. 
Marenzeller, F. yon. 

'79. Die Aufzucht des Badeschwamms aus Theilstticken. Verb. Zool.-bot. Ges. Wien., 
XXXVIII, 1879. 
Martinotti, C. 

'90. liber Hyperplasie und Regeneration der driisigen Elemente in Beziehung auf ihre 
Functionsfahigkeit. Centralbl. f. allg. Pathol., I, 1890. 
Martins, E. yon. 

'66. ijber ostasiatische Echinodermen. Archiv. f. Naturgesch., L, 1866. 
'84. Uber das Wiedererzeugungsvermogen bei Seestemen. Sitz. d. Gesell. naturf. 
Freunde zu Berlin, 1884. 
Mayer, C. 

'59. ReproductionsvermSgen und Anatomie der Naiden. Ver. Nat. Vereins, Rheinlande 
XVI, 1859. 
Mazza, F. 

*90. Sulla ringenerazione della pinna caudale in alcuni Pesci. Atti Soc. Ligust. Sc. N., 
1,1890. 
Michel, A. 

'98. Recherches zur la regeneration chez les Annelides. Bull. Sc. France et Belg., 
XXXI, 1898. 
Mingazzini, P. 

*9i. Sulla rigenerazione nei Tunicati. Boll. Soc. Napoli, V, 1891. 
Monti, R. 

'cx>. Studi Sperimentali sulla Regenerazione nei Rebdoceli marini. Rendiconti d. R. 

Inst. Lomb. Sc. e Lett., (Ser. II,) XXXIII, 1900. 
^QO. La ringenerazione nelle Planarie marine. Mem. R. Inst. Lomb. Sc. Lett. G. Sc. 
Mat. Nat., XIX, 1900. 
Morgan, T. H. 

*93. Experimental Studies on the Teleost Eggs. Anat. Anz., VIII, 1893. 

'93. Experimental Studies on Echinoderm Eggs. /bid,y IX, 1893. 

'95. A Study of Metamerism. Q. J. Micr. Sc, XXXVII, 1895. 

'95. The Formation of the Fish Embryo. Jour. Morph., X, 1895. 

'95. Half Embryos and Whole Embryos from one of the first two Blastomeres of the 

Frog's Egg. Anat. Anz., X, 1895. 
'95. A Study of a Variation in Qeavage. Arch. f. Entw.-mech., II, 1895. 
'95. Studies of the " Partial " Larvae of Sphaerechinus. find., II, 1895. 
'95. The FertiHzation of non-nucleated Fragments of Echinoderm-Eggs. Ibid,, II, 1895. 
'96. The Number of Cells in Larvae from Isolated Blastomeres of Amphioxus. Ibid,, III, 

1896. 
'97. Regeneration in Allolobophora foetida. Ibid., V, 1897. 
'97. The Development of the Frog's Egg. New York, 1897. 
'98. Developmental Mechanics. Science, N. S., VII, 1898. 

'98. Experimental Studies of the Regeneration of Planaria maculata. Arch. f. Entw.- 
mech., VtlL 1898. 
'98. Regeneration and Liability to Injury. Zool. Bulletin, I, 1898. 
'99. Regeneration of Tissue composed of Parts of Two Species. Biol. Bulletin, I, 1899. 
'99. Regeneration in the Hydromedusa, Gonionemus vertens. The American Natu- 
ralist, XXXIII, 1899. 

Digitized by LjOOQIC 



304 REGENERATION 

'99. A Confirmation of Spallanzani's Discovery of an Earthworm regenerating a Tail in 

place of a Head. Anat. Anz., XV, 1899. 
'99. Further Experiments on the Regeneration of Tissue composed of Parts of Xwro 

Species. Biol. Bulletin, I, 1899. 
'99. Some Problems of Regeneration. Biological Lectures, Woods Holl (1898), 1899. 
'cx>. Further Experiments on the Regeneration of the Appendages of the Hermit-Cr&b. 

Anat. Anz., XVII, 19CX). 
'00. Regeneration: Old and New Interpretations. Biological Lectures, Woods Holl 

(1899), 1900. 
*oo. Regeneration in Bipalium. Arch. f. Entw.-mech., IX, 1900. 
'00. Regeneration in Planarians. Ibid.^ X, 1900. 
'00. Regeneration in Teleosts. Ibid,^ X, 1900. 
'01. Regeneration in Tubularia. Ibid,^ XI, 1901. 
'01. The Problem of Development. The International Monthly, 1901. 
'01. The Factors that determine Regeneration in Antennularia. Biol. Bulletin, II, 1 90 1. 
'01. Regeneration of Proportionate Structures in Stentor. Biol. Bulletin, II, 1901. 
'01. Regeneration in Planaria lugubris. Arch. f. Entw.-mech., XII, 1901. 
Morgan, T. H., and Tsuda, Um£. 

'93. The Orientation of the Frog's Egg. Q. J. Micr. Sc., XXXV, 1893. 
Miiller, E, 

'96. Uber die Regeneration der Augenlinse nach Extirpation derselben bei Tritonen. 
Arch. f. mikr. Anat., XLVII, 1896. 
Miiller, F. 

'80. Haeckel's Biogenetische Grundgesetz bei der Neubildung verlorener Glieder. 
Kosmos, VIII, 1880-81. 
Miiller, E. 

'95. Uber das Wiederwachsen (Regeneration) von Korperteilen. Jahresb. d. Ver. f. 
vaterl. Naturk. in Wurttemberg, LVI, i89«^. 
Miiller, H. 

'64. Uber Regeneration der Wirbelsaule und des Rackenmarkes bei Tritonen und £!• 
dechsen. Frankfurt a. M., 1864. 
MiUler, 0. F. 

1771. Von Wiirmern des siissen und salzigen Wassers. 1771. 
Nageli, C. von. 

'84. Mechanisch-physiologische Theorie der Abstammungslehre. 1884. 
Newport, 6. 

'44. On the Reproduction of Lost Parts in Myriapoda and Insecta. Phil. Trans., 1844. 
Nussbaum, M. 

'84. Uber spontane und kiinstliche Zellteilung. Sitz. d. Niederrh. Ges., 1884. 

'86. Uber die Teill)arkeit der lebendigen Materie. I. Die spontane und kQnstliche 

Teilung der Infusorien. Arch. f. mikr. Anat., XXVI, 1886. 
'87. Uber die Teilbarkeit, etc. II. Beitrage zur Naturgeschichte des Genus Hydra. 

Arch. f. mikr. Anat., XXIX, 1887. 
'91. Mechanik des Trembleyschen UmstGlpungsversnchs. Arch. f. mikr. Anat., XXXVI, 

1891. 
'94. Die mit der Entwickelung fortschreitende Differenzierung der Zellen. Sitz.-Ber. 
Niederrh. Ges. Bonn, 1894. 
Nussbaum, J., and Sidoriak, S. 

'90. Beitrage zur Kenntnis der Regenerations vorgange nach Kunstlichen Verletzungen 
bei alteren Bachforellen embryonen (Salmo fario. L.). Arch. f. Entw.-mech., X, 1890. 
Parke, H. H. 

'cx>. Variation and Regulation of Abnormalities in Hydra. Arch. f. Entw.-mech., X, 1900. 
Parker, 6. H., and Burnett, F. L. 

'00. The Reactions of Planarians with and without Eyes to Light. Am. Journ. Physiol., 
IV, 1900. 



Digitized by LjOOQIC 



LITERATURE 305 

Parona, C. 

'91. L'Autotomie c la regeneratione delle appendici dorsale nella Tethys lepornia. 

Atti della R. Universita di Genova, VII, 1891. (Also Zool. Anz., XIV, 1891.) 
Peeblea, Florence. 

*97. Experimental Studies on Hydra. Arch. f. Entw.-mech., V, 1897. 

'98. The Effect of Temperature on the Regeneration of Hydra. Zool. Bull., II, 1898. 

'00. Experiments in Regeneration and in Grafting of Hydrozoa. Arch. f. Entw.-mech., 

X, 1900. 

Perrier, Ed. 

'72. Recherches sur I'Anatomie et la Regeneration des Bras de la Comatula rosacea. 

Arch. Zool. Experim., II, 1872. 
'73. Sur TAutotomie et la Regeneration des Bras de la Comatula. Arch. Zool. Experim., 
II, 1873. 
Peters, A. 

'89. Uber die Regeneration des Endothels der Cornea. Arcii. f. Mikr. Anat., XXXIII, 
1889. 

Petrone, A. 

'84. Du processes regenerateur sur le poumon, sur la foie et sur le rein. Archiv. Ital. 
d. Biol., V, 1884. 
Pfeffer, W. 
ibaTci' ,^^^ Pflanzenphysiologie, 1897. 

Pfliiger, E. 

'77. pie teleologische Mechanik der lebendigen Natur. Pfluger's Arch., XV, 1877. 
'83. tjber der Einfluss der Schwerkraft auf die Teilung der Zellen. Pfliiger's Arch. , 

XXXI, 1883. 
'83. tJber den Einfluss der Schwerkraft auf die Teilung der Zellen und auf die Entwick- 

elung des Embryos. Pfluger's Arch., XXXII, 1883. 
'84. tJber die Einwirkung der Schwerkraft und anderer Bedingungen auf die Richtung- 

der Zellteilung. Pfluger's Arch., XXXIV, 1884. 

«^* Phillipeaux, J. M. 

'66-'67. Experience demontrant que les membres de la salamandre aquatique (Triton 

cristatus) ne se regencrent, etc. Compt. Rend. d. TAcad. de Science, 1866-67. 
'67. Sur la regeneration des membres chez TAxolotl (Siren pisciformis). Ibid,^ 1867. 
'74. Note sur les resultats de Textirpation complete d*un des membres anterieurs sur 

TAxolotl et sur la salamandre aquatique. Gaz. Med. de Paris, 1874. 
'76. Experiences montrant que les mamelons extirpes sur des jeunes Cochons d'Inde ne 
jSj, se regencrent point. Compt. Rend., 8 Fev., 1876. 

'76. Les membres de la salamandre aquatique bien extirpes ne se regencrent point, 

Compt. Rend., LXXXII, Nr. 20, 1876. 
^- '79. Note sur la regeneration de I'humeure vitree chez les animaux vivant, lapins, 

cochons d'Inde. Gaz. M6d. de Paris, 1879. 
'79. Sur la retablissement de la vue chez les cochons d'Inde aprCs Textraction des hu- 

meurs vitr6e et cristalline. Gaz. Med. de Paris, 1879. 
*8o. Note sur la production de Toeil chez la salamandre aquatique. Gaz. Med. de Paris, 

1880. 

Plana, 6. 

'94. Ricerche sulla polidactilia acquisita determinala sperimentale nei tritoni e sulla 
coda supernumera nelle lucertole. Ric. Lab. di Anat. norm, di Roma, IV, 1894. 

Pliny, Secundos. 

77. Secundi historia mundi. Lib. XXXVII, Lib. XI. 

Ponfick, E. 

*90. iJber Rekrcation der Leber. Verhandl. des X Intern. Kongresses zu Berlin, II, 1890, 

Porta, Jo. Baptista. 

1650. Neapolitani magiae naturalis libri viginti. Rhotomagi MDCL, Lib. II. 

Digitized by VjOOQIC 



306 REGENERATION^ 

Prantl, K. 

' 74. Untersuch. fiber die Regeneration des Vegetations-ponktes an AngiospermenwurzeliL 
Arb. a. d. Bot. Instit in Wurzburg, IV, 1874. 
Prejrer, W. 

'86. Uber die Bewegungen der Seesteme. Mitth. ZooL Stat. Neapol, VII, 1886-87. 
Pringsheim, 6. 

'76. Uber Vegetative Sprossen der Moosfruchte. Monatsberichte d. k. Akad. d. Wias. 
zu Berlin, Juli, 1876. 
Przibram, H. 

'96. Regeneration bei den Crustaceen. Zool. Anz., XIX, 1896. 
'99. Die Regeneration bei den Crustaceen. Arb. d. Zool. Inst, in Wien., II, 1899. 
'00. Experimentelle Studien iiber Regeneration. Biol. Centralbl., XX, 1900. 
Quatrefages, A. 

'65. Histoire naturelle des Annelees. I (page 126), 1865. 
Rand, H. W. 

*99. Regeneration and Regulation in Hydra viridis. Arch. f. Entw.-mech., VIII, 1899. 
'99. The Regulation of Graft-Abnormalities in Hydra. Arch. Entw.-mech. IX, 1899. 
Randolph, Harriet. 

*92. The Regeneration of the Tail in Lumbriculus. Jour. Morph., VII, 1892. 
'97. Observations and Experiments on Regeneration in Planarians. Arch. f. Entw.^ 
mech., 5, 1897. 
Rankin, D. R. 

'57. On the Structure and Habits of the Slowworm (Anguis fragilis Linn.). Edin- 
burgh New Philos. Jour. (N. S.), V, 1857. 
Rauber, A. 

'95. Die Regeneration der Krystalle, I. Leipzig, 1895. ^^> 1896. 
Reaumur, R. A. de. 

1 71 2. Sur les divers^es Reproductions. Mem. d. TAcad., 171 2. 
1742. Memoires pour servir a I'histoire des Insectes. Tome VI, Preface, 1742. 
Ribbert, H. 

*94. Beitrage zur kompensatorischen Hypertrophie und zur Regeneration. Arch. f. 

Entw.-mech. I, 1894. 
*97. liber Veranderungen transplantierter Gewebe. Arch. f. Entw.-mech. VI, 1897. 
*97. iJber Riickbildung an Zellen und Geweben und fiber die Entstehung der Ge- 

schwulste. Bibl. med. Abt., C, 1 897. 
'98. Uber Veranderungen der abnorm. gekrummten Schwanzwirbelsaule des Kanin- 

chens. Arch, f. Entw.-mech., VI, 1898. 
'98. Uber Transplantation von Ovarium, Hoden, und Mamma. Arch. f. Entw.-mech., 
VII, 1898. 
Rieyel, H. 

'96. Die Regeneration des Vorderdarms und Enddarms bei einigen Anneliden. Zeit. 
wiss. Zool., LXII, 1896. 
Ritter, W. £., and Congdon, £. M. 

'00. On the Inhibition by Artiticial Section of the Normal Fission Plane in Stenostoma. 
Proc. California Acad. Science, II, 1900. 
Rothig, P. 

'98. Ober Linsenregeneration. Inaug.-Diss. Berlin, 1898. 
Roux, W. 

'83. Uber die Bedeutung der KernteilungsBguren. Leipzig, 1883. 

'85. Beitrage zur Entwickelungsmechanik des Embryo. I. Zur Orientierung fiber einige 

Probleme der embryonalen Entwickelung. Zeit. f. Biologie, XXI, 1885. 
*84. II. Uber die Entwickelung des Froscheies bei Aufhebung der richtenden Wirkung 

der Schwere. Breslauer aerztl. zeitsch., 1884. 
'85. III. Uber die Bestimmung der Hauptrichtungen des Froschembryo im Ei und 
fiber die erste Teilung des Froscheies. Ibid.^ 1885. 



Digitized by LjOOQIC 



UTERATURE 307 

'87. IV. Die Bestimmung der Medianebene des Froschembryo durch die Kopulations- 

richtung des Eikernes and des Spermakernes. Arch. f. mikr. Anat> XXIX, 1887. 
^^, V. Ober die kiinstliche Hervorbringung halber Embryonen durch Zerstorung einer 

der beiden ersten Furchungskugeln, etc. Virchow's Archiv, CXIV, 1888. 
'91. VI. Uber die morphologische Polarization von Eiern und Embryonen durch den 

elekirischen Strom. Sitz. Ber. Akad. Wiss. Wien., CI, 1891. 
'90. Die Entwickelungsmechanik der Organismen, eine anatomische Wissenschaft der 

Zukunlt. Wien, 1890. 
'92. (Jber das entwickelungsmechaniache Vermogen jeder der beiden ersten Furchungs- 

zellen des Eies. Verhandl. Anat. Gesell. Wien., 1892. 
'93. Ober Mosaikarbeit und neuere Entwickelungshypothesen. Anat. Hefte, 11, 1893. 
'93. Ober die Spezifikation der Furchungszellen und iiber die bei der Postgeneration 

und Regeneration anzunehmenden Vorgange. Biol. CentralbL, XIII, 1893. 
'94. Ober den Cytotropismus der Furchungszellen des Grasfrosches. Arch. f. Entw.- 

mech., I, 1894. 
'95. Gesammelte Abhandlungen flber Entwickelungsmechanik. Leipzig, 1895. 
*95. Ober die verschiedene Entwickelung isolierter erster Blastomeren. Arch. f. 

Entw.-mech., I, 1895. 
'96. Ober die Selbstordnung (Cytotaxis) sich berClhrender Furchungszellen, etc. Ibid,, 

III, 1896. 

'96. Ober die Bedeutung "geringer" verschiedenheiten der relativen Grosse der 

Furchungszellen fiir den Charakter des Furchungsschemas. Ibid,, IV, 1896. 
'97. Fur unser Programm und seine Verwirklichung. Ibid,, V, 1897. 
'96. Zu H. Driesch's " Analytischer Theorie der organtschen Entwickelung." Ibid,, 

IV, 1896. 

'00. Berichtigungen zu O. Schultze's jiingstem Anfsatz fiber die Bedeutung der 
Schwerkraft, etc. Ibid,, X, 1900. 
Sachs, J. 

'80. StofF und Form der Pflanzenorgane. Arbeiten d. hot. Instituts WCirzburg, II, 

1880-82. 
'93. Physiologische Notizen, I. Flora, 1893. 
Sansin, P. and F. 

'88. Knospenbildung bei Linckia multiformis. Ergebn. Naturforschung auf Ceylon, 
1884-85. I. Wiesbaden, 1888. 
San, G. 0. 

'75. Researches on the Structure and Affinity of the Genus Brisinga. Christiania, 1875. 
Schaper, A. 

'98. Experimentelle Studien an Amphibienlarven. I. Haben kunstlich angelegte De- 
fekte des Centralnervensystems oder die vollstandige Elimination desselben einen 
nachweisbaren Einfluss auf die Entwickelung des Gesamtorganismus junger Frosch- 
larven? Arch. f. Entw.-mech., VI, 1898. 
Schiedt, R. R. 

'92. Diffuse Pigmentation of the Epidermis of the Oyster due to prolonged exposure to 
Light. Regeneration of Shell and loss of Adductor Muscle. Proc. Acad. Nat Sci. 
Phila., 1892. 

Schimkewitsch, W. 

'00. Ober einer Fall von Heterotopie der Haare. Verb. d. k. Naturforscher Gesell. in 
St. Petersburg, XXX, 1900. 

Schmidt, E. 0. 

'75. Spongien. Jahresb. Comm. Untersuch. Deutschen Meere in Kiel, II und III, 
Jahrg., 1875. 
Schoatakowitsch. 

'94. Ober Regeneration, etc., bei Lebermoosen. Flora, Erganzungsband, 1894. 
Schnltz, E. 

'98. Ober die Regeneration von Spinnenf^en. Trav. Soc. Nat. Petersb., XXIX, 1898. 



Digitized by VjOOQIC 



308 REGENERATION 

Schnltze, E. 

'99. A118 dem Gebiete der Regeneration. Zeit. f. wiss. Zool., LXVI, i899« 

Schnltze, L. 8. 

'99. Die Regeneration des Ganglion von Ciona intestinalis, L. nnd iiber das Verhaltnis 
der Regeneration and Knospung zur Keimblatterlehre. Jena Zeit. f. Naturwia^ 
XXXIII, 1899. 
Schnltze, 0. 

'94. Die kdnstliche Erzeugung von Doppelbildungen bei Froschlarven mit Hnlfe ab- 

normer Gravitationswirkung. Arch. f. Entw.-mech., I, 1894. 
'99, t3ber das erste Auftreten der bilateralen Symmetric im Verlauf der Entwickelnng. 

Archiv. f. Mikr. Anat., LV, 1899. 
'99. Ober die Nothwendigkeit der freien Entwickelung des Embryo. Ibid^ 1899. 
Sciidder, S. 

*68-*69. Proceedings Boston Society of Natural History (page 99), XII, 1868-69. 
Semon, R. 

'89. Neubildung der Scherbe in der Mitte eines abgebrochenen Seestemarmes. Jena. 
Zeit. f. Naturw., XXlll, 1889. 
Semper, C. 

'68. Reisen in Archipel der Philippinen, II, 1868. 

'76. Die Verwandtschaftsbeziehungen der gegliederten Thiere. Arb. zool.-zoot. Inst. 
WUrzburg, III, 1876, 
Siebold. 

*28. Observationes quaedam de Salamandris et Tritonis. Diss. Berolini, 1828. 
Simroth, H. 

'77. Anatomie und Schizogonie der Ophiactis virens. Zeit. f. wiss. Zool., XXVIII, 1877. 
SpalUnzani, L. 

1782. Risultati di esperienze sopra la riproduzione della Testa nelle Lumache Terrestri. 

Memoria di Matematica e Fisica della Societa italiana, tomo I, Verona, 1782. 
'26. Prodromo di un' opera sopra le riproduzioni animali. Milano, 1826. 
Spemann, H. 

'00. Experimentelle Erzeugung zweikdpfiger Embryonen. Sitzber. d. Phys. Med. 

Gesell. Wurzburg, 1900. 
'01. Entwickelungsphysiologische Studien am Triton-Ei. Archiv. f. Entw.-mech., XII, 
1901. 
Spengel, J. W. 

'93. Monographic der Enteropneusten. Fauna und Flora des Golfes von Neapel, 1893. 
Stahl, E. 

'76. Cber kfinstliche hervorgerufene Protonemabildungen an dem Sporogonium der 
Laubmoose. Bot. Zeit., 1876. 
Strasser, H. 

'99. Regeneration und Entwickelung. Berner Rektoratsrede. Jena, 1899. 
Studer, Th. 

'77. Echinodermen aus dem antarktischen Meere. Monatsber. d. Berliner Akad., 1877. 
Tittmann, H. 

'95. Phvsiol. Untersuch. fiber Callusbildung an Stocklingen. Jahr. f. wiss. Botan., 
XX VIII, 1895. 
Tizzoni, 6. 

'83. Experimentelle Studie fiber die partielle Regeneration und Neubildung von Lebep- 
gewebe. Biol. Centralb., Ill, 1883-84. 
Tornier, 6. 

'96. Ober Hyperdaktylie, Regeneration und Vererbung mit Experimenten. Arch. f. 

Entw.-mech., Ill, 1896. 
'97. Uber expcrimentell erzeugte dreischwanzige Eidechsen und Doppelgliedmassen 
, von Molchen. Zool. Anz., XX, 1897. 



Digitized by LjOOQIC 



LITERATURE 309 

'97. t)ber Operationsmethodei], welche sicher Hyperdaktylie erzeugen mit Bemerkungen 
uber Hyperdaktylie und Hyperpedie. Zool. Anz., XX, 1897. 
Tower, W. L. 

lii^^ '99. Loss of the Ectoderm of Hydra viridis in the Light of a Projection Microscope. 

The American Naturalist (page 505), June, 1899. 
Towle, E. W. 

'91. On Muscle Regeneration in the Limbs of Plethedon« Biol. Bull., II, 1891. 
g&i> Trembley, A. 

'74. Memoires pour servir k Phistoire d'un genre de Polypes d'eau douce. Leide, 1774. 
i^ TyUer, R. C. 

'65. Farbenwechsel, die HSutung und die Regeneration des Schwanzes bei den Ascala- 
^ boten. Journ. of the Asiatic Soc. of Bengal, 1865. 

Vernon, H. M. 
^ '99. The Effect of Staleness of the Sexual Cells on the Development of Echinoids. 

Proc. Roy. Soc, LXV, 1899. 
fgi '00. Cross-Fertilization among Echinoids. Arch. f. Entw.-mech., IX, 1900. 

Verwom, M. 

'91. Die physiologische Bedeutung d. Zellkems. Arch. f. d. ges. Physiol., LI, 1891. 
'88. Biologische Protistenstudien. I. Zeit. f. wiss. Zool., XLVI, 1888. 
l^ '89. Psycho-physiologische Protistenstudien, 1889. 

'89. Die Polare Erregung der Protisten durch den galvanischen Strom. Arch. f. d. ges. 
Physiol., XLVI, 1889. 
Vochting,H. 

*77. (Jber die Teilbarkeit und die Wirkung innerer und ausserer Krafte auf die Organ- 
, j5^ bildung in Pflanzenteilen. Pfiiiger's Arch., XV, 1877. 

'78. Ober Organbildung im Pflanzenrciche. Bonn, 1878 u. 1884. 
'85. yber die Regeneration der Marchantieen. Jahrb. f. wiss. Botanik, XVl, 1885* 
^ '87. Ober die Bildung von KnoUen. Bibliotheca Botanica, No. 4, Cassel, 1887. 

'92. Ober Transplantation am Pflanzenk6rper. Tiibingen, 1892. 
I Voigt,W. 

'99. KQnstlich hervorgerufene Neubildung von k5rpertheilen bei Strudelwurmern, 
. ^'* Sitz. d. Niederrhein. Gesell. f. Natur- und Heilkunde zu Bonn, 1899. 

^ De Vries, H. 
w^^ *89. Intracellulare Pangenesis, 1889. 

▼ulpian, M. A. 

'59. Notes sur les phenom^nes de developpement qui se manifestent dans la queue de 
»^^* tr^ jeunes embryons de grenouille. Compt. Rend., XLVIII, 1859. 

^ Wagner, F. von. 
^ '^, *93* Einige Bemerkungen uber das Verhaltnis von Ontogenie und Regeneration. Biol. 

Centralbl., XIII, 1893. 
'97. Zwei Worter zur Kenntniss der Regeneration des Vorderdarms bei Lumbriculus. 

Zool. Anz., XX, 1897. 
'00. Beitrage zur Kenntniss der Reparationsprozesse bei Lumbriculus variegatus. I. 
yr Zool. Jahrb., XIII, 1900. 

Wagner, W. 
\ijOi' '87. La regeneration des organes perdus chez les araignees. Bull. Soc. Imp. Natural., 

Moscow, 1887. 
Watson, J. 
p^ '91. On the Redevelopment of Lost Limbs in the Insecta. The Entomologist, XXIV, 

1891. 
Weiamann, A. 
jA i *9i. Essays on Heredity, Vol. I. Qarendon Press, Oxford, 1891. 

*92. Das Keimplasma. Eine Theorie der Vererbung. Jena, 1892. 
^ '94. The Germ-plasm. New York, 1894. 

'96. Uber Germinal-Selektion. Eine Quelle bestimmtgerichteter Variation. Jena, 1896. 

Digitized by VjOOQIC 



310 REGENERATION 

'97. Regeneration : Facts and Interpretations. Natural Science, April, 1S97. 

'99. Thatsachen und Auslegungen in Besug aof Regeneration. Anat. Anz., XV, 1899. 
Wendelstadt, H. 

'01. Dber Knochenregeneration. Arch. f. mikr. Anat., LVII, 1801. 
Werner, F. 

*92. Selbstverslummelung bei Heuschrecken Zool. Anz., XV, 1892. 

'96. Uber die Schuppenbildung des regenerierten Schwanzes bei Eidechsen. Sitz- 
ungsber. d. kais. Akad. in Wien, CV, 1896. 
Wetzel, 6. 

'95. Transplantationsversuche mit Hydra. Arch. f. mikr. Anat., XLV, 1895. 

'95. Ober die Bedeotung der cirkul&ren Furche in der Entwickelung der Schultzeschen 
Doppelbildungen von Rana Fusca. Arch. f. mikr. Anat., XLVI, 1895. 

'96. Bcitrag zum Studium der kUnstlichcn Doppelmissbildungen von Rana Fusca. 
Inaug. Dissert., 1896. 
Whitman, C. 0. 

'89. The Seat of Formative and Regenerative Energy. Jour. Morph., II, 1889. 

'93. The Inadequacy of the Cell Theory of Development Jour. Morph., VIII, 1893. 

'95. Evolution and Epigenesis. Biolog. Lectures at Woods HoU in 1894, 1895. 
Wiedersheim, R. 

'77. (jber Neubildung von Kiemen bei Siren lacertina. Morph. Jahrb., Ill, 1887. 
Wilson, C. B. 

*97. Experiments on the Early Development of the Amphibian Embryo under the Influ- .^ 

ence of Ringer and Salt Solutions. Arch. f. Entw.-mech., V, 1897. in 

'00. The Habits and Early Development of Cerebratulus Lacteus. Q. J. Mic Sc^ i 

XLIII, 1900. ^ 

Wilson, E. B. \^ 

'92. The Cell-Lineage of Nereis. Jour. Morph., VI, 1892. \ 

'93. Amphioxus and the Mosaic Theory of Development. Jour. Morph., VIII, 1893. 4 

'95. On Cleavage and Mosaic Work. Appendix to Cramplon. Arch. f. Entw.-mech., \ 

III, 1895. 1 

'96. The Cell in Development and Inheritance. New York and London, 1896. 

'98. Considerations on Cell-Lineage and Ancestral Reminiscence. New York Acad. 

Science, II, 1898. 
Wolff, G. 

'94. Bemerkungen zum Darwinismus mit einem experimentellen Bcitrag zur Physiologic 

der Entwickelung. Biol Centralbl., XIV, 1894. 
'93. Entwickelungphysiologische. Studien. I. Die Regeneration der Urodelenlinse. ^ 

Arch. f. Entw.-mech., I, 1893. 
Zacharias, 0. 

'86. Ober Fortpflanzung durch Spontanquertheilung, etc. Zeit. f. wiss. Zool., XLIII, 

1886. 



h 



A 
.\ 
K 
A 

Ziegler, E. ^ ^ 

'91. tjber die ursachen der pathologischen Gewebsneubildungen. International Bei- 
trage zur wissenschaftliche Medizin. Festschrift fur Virchow, II, 1891. 
Ziegler, H. E. 

'98. Experimentelle Studien uber die Zellteilung, I. Die Zerschnurung der Seeigeleier. j 

Arch. f. Entw.-mech., VI, 1898. t j 

'98. Experimentelle Studien, etc.. III. Die Furchungszellen von BeroS ovata. Arch. ' 1 

f. Entw.-mech., VII, 1898. j 

Zoja, R. I 

'95. Sullo sviluppo dei blastomeri isolati delle uova di alcune meduse. Arch. f. Entw.* ' 1 

mech., I u. II, 1 895. 



Digitized by LjOOQIC 



INDEX 



Accidental Regeneration, 25. 
Achimenes, 88. 
Actinians, 142. 

Actinosphserium eichhornii, 65. 
"Action at a distance," 283-287. 
Adaptation, 94, 158, 277, 288-292. 
Allman, 38. 

Allolobophora terrestris, 172, 174, 175. 
Alpheus platyrrhynchus, 63. 
Amoeba, 103. 
Amphibia, 106. 
Amphioxus, 105, 139, 231, 237. 
Amphiuma, 106. 

Analytische Theorie of Driesch, 253-254. 
Andrews, E. A., 152. 
Andrews, Mrs. G. F. 251. 
Anguis fragilis, 198. 
Annelids, 104, 143. 

Antennularia antennina, 30-33, 103, 131. 
Ants, 154. 
Aristotle, i. 
Aschoff, 115. 
Ascidian, 114, 149. 
Ascidian egg, 236. 
Asplenium, 23. 
Aster ias vulgaris, 102, 103. 
Atrophy, in, 123-125. 
AtyuTda potimirum, 24, 2 1 3. 
Aurelia, 104. 
Autolytus, 143. 

Autotomy, no, 142, 150-155; theories of, 
155-158. 

Baer, von, 208. 

Balbiani, 66, 129. 

Bardeen, 41, 136. 

Barfurth, 21, 45, 54, 129, 137, 197, 199, 

200. 
Begonia, 23; B. discolor, 74. 
Beneden, Van, 210. 
Berog ovata, 239. 
Bert, 178. 

Bickford, E., 57, 202. 
Biophors, 278. 



3" 



Bipalium, 13, 14, 104; grafting, 170. 

Birds, 97, 106. 

Bizozzero, 128. 

Blastomeres, 19, no. 

BlastuUe, fusion of, 188. 

Blood vessels, 120, 122-123. 

Blumenbach, 112. 

Bock, von, 149. 

Bombinator igneus, 184. 

Bones, 113^ 124, 181. 

Bonnet, I ; experiments with worms, 2, 26, 

38, 41, 92, 112, 200, 260, 261, 267. 
Bordage, 97, 100, 157. 
Born, 182-183, 243. 
Boulenger, 214. 
Boveri, 68, 228. 
Braefeld, 17, 80. 
Braem, 211. 
Brandt, 65. 

Breaking-joint, 150-152. 
Brindley, 100, 104. 
Brittle-stars, 105, 144, 145. 
Broussonet, 97. 
Bryozoa, 211. 
Budding, 142, 1 49-1 50. 
Bulow, 190, 213. 
Bunting, 237. 
Byrnes, 182. 

Callus, 82, 83. 

Camerano, 92. 

Campanularia, 35. 

Carniola, 106. 

Carodina, 213. 

Carriere, 104, 2 1 3. 

Cat, 179. 

Caterpillar, loo, 104, 154. 

Cause, 287, 290. 

Cells, origin of, 190-215. 

Cephalodiscus, 149. 

Cerianthus membranaceous, 41, 104. 

Cermatia forceps, 100. 

Cestodes, 103, 146. 

Chabry, 236. C" r^r^n]i> 

Digitized by ^^OOy LC 



312 



INDEX 



Chaetogaster, 146. 

Chaetopterus, 189. 

Chun, 238. 

Ciona intestinalis, 42. 

Closing wound, 69. 

Cockroach, 100, 104. 

Coelenterates, 145, 149. 

Cohnheim, 118, 119. 

Colucci, 112, 203. 

Conifers, 76 (footnote). 

Conklin, 116. 

Connective tissue, 180, i8i. 

Contact, 33, 37. 

Coprinus stercorarius, 86, 87* 

Corals, 142. 

Crab, 43, 151, 152, 158. 

Crampton, 236, 240, 245* 

Crayfish, 100, 151, 157. 

Crepidula fornicata, 116. 

Crinoids, 105. 

Crystal, regeneration of, 263-264. 

Ctenodrilus monostylos, 144, 148. 

Qenodrilus pardalis, 144, 148. 

Ctenophore-egg, 238-241. 

Qenophores, 142. 

Cuvierian organs, 105. 

Cytotropism, 69, 281. 

Daly ell, 129, 144. 

Darwinism, 108. 

Darwin's pangenesis, 278. 

Delage, 25, 92. 

Dendroccelum, 104. 

Difflugia, 103. 

Double structures, 128, 135-141. 

Driesch, definition of regeneration, 21, 22; 
reparation, 22; regulation, 22; restitu- 
tion, 22; self-regulation, 22; antennu- 
laria, 32; 43, 57, 59, 60, 135, 139, 188, 
202, 228-236, 243, 246, 248, 250, 251, 
252-255, 257, 267, 268, 274, 280, 281- 
287. 

Driesch and Morgan, 239-241, 245. 

Du Bois-Reymond, 286. 

Duges, 136. 

Duhamel, 178. 

Duyne, van, 136, 140, 141. 

Dwarfs, 116. 

Earthworm (Allolobophora foetida), 9, 12, 
38-39, 40, 53, 144, 170, 194, 271, 280, 
290. 

Echinoderms, 105, 144. 

Echinus microtuberculatus, 68. 

Egg, 18, 19, I39» 188, 216. 



Embryo, 18, IIO) 216; grafting in, 182- 
189; union of, 188; tension hypothesis, 

274. 
Endres, 221. 
Epeiridae, 100. 
Epimorphosis, 23. 
Epithelium, 180. 

Eudendrium racemosum, 29, 30, 103. 
External factors, 26. 
Eye, 203; Crustacea, 30; lens, 203-205. 

Factors, 277. 

Faraday, 136. 

Fiedler, 228. 

Fischel, 112, 205-207, 240, 291, 292. 

Fischer, 124, 178. 

Fish, 6, 97, 131-133. 274, 281; lens, 29a. 

Fish's eggs, 237. 

Flatworms, see Flanarians. 

Food, influence of, 27, 37, 120, 122, 123. 

Force, 76, 287. 

Formative forces, 255, 277, 288. 

Formative stuffs, 40, ^ 89, 90, 91. 

Fraisse, 21, 97, 196, 197, 198, 199, aoo^ 214. 

Fredericq, 151, 152. 

Frogs, 106. 

Frogs' egg, 216. 

Fundulus eggs, 237. 

Fundulus heteroclit'us, 45, 97, 274. 

Gastroblasta Raffsclei, 142, I45. 

Gerassimoff, 66. 

Germ-layers, 207-212. 

Giants, 115. 

Giard, 92. 

Godelmann, 154. 

Goebel, 22, 85, 86, 88, 89, 9a 

Goette, 106, 200, 201, 213. 

Gonionemus, 104, 125. 

Grafting, 159-189. 

Gravity, influence of, 30-33, 37. 

Grawitz, 119. 

Growth, 128, 131-135, 269-271, 278, 292. 

Gruber, 66. 

Guinea pig, 179. 

Haberlandt, 66. 
Haeckel, 102, 208, 216. 
Half-embryos of frog, 216-226. 
Hargitt, 125, 127, 168, 169. 
Harmony, 282. 
Harrison, 186, 187. 
Heart, 124. 
Heineken, 100. 
Helicarion, 93. 



Digitized by LjOOQIC 



INDEX 



313 



Heliotropism, 271* 

Hepke, 190, 192. 

Herbst, 30, 214, 286. 

Hermit-crab, 63, 97^-99; autotomy, 155 

Hcrrick, 153. 

Hcrtwig, O., 22, 23, 222-227, ^3» 246, 251, 

252, 256, 278, 280, 2^. 
Hcrtwig, R., 228. 
Hescheler, 44, 194, 196. 
Heterocentron diversifoliam, 74, 8a 
Heteromorphosis, 24, 38-42. 
Heteronereis, 143. 
Heterotropy, 280. 
His, 241. 
Hjort, 210. 
Hofer, 66. 
Holomorphosis, 24. 
Holothurians, 105, 145, 154. 
Homology, 209. 
Homomorphosis, 23. 
Hunter, 178. 
Huxley, 208. 

Hyacinthus orientalis, 88. 
Hydra, I, 2, Ii, 56, 103,121,122,124,142, 

149; grafting, 159-166, 203, 270, 272. 
Hydra grisea, 169. 
Hydra fusca, 169. 
Hydractinia, 103, 16& 
Hyperplasy, 115. 
Hypertrophy, in, 115-123. 

Idiosomes, 278. 
Ilyanassa obsoleta, 240. 
Internal factors, 38, etc., 52-54* 
Internal organs, 52-54, III. 
Iris, 204-207. 
Ischikawa, 203. 

Jelly-fish's eggs, 237, 
Joest, 170-175, 186. 

Kennel, von, 147, 148, 149. 

Kidney, 113, 116, 124, i8o» 

King, 102, 103, 125, 135, 139, 153, 162, 214. 

Klebs, 66, 118, 120. 

Knight, 75. 

Knowlton, 27. 

Kochs, W., 112. 

Kowalevsky, 208, 210. 

Kret?, 112. 

Kroeber, 196. 

Lamarckianism, 157. 

Langi 92, 93- 

Lateral Regeneration, 9, 10, 28, 29, 43. 



Leeches, 146. 

Lefevre, 210, 211. 

Lepelletur, 100. 

Lepismlum radicans, 78. 

Lessona, 92, 93. 

Liability to injury, 92-1 10; view of R6aumur, 

92;. of Bonnet, 92; of Darwin, 92; of 

L*ng» 93; of Semper, 93; of Weismann, 

93-96. 
Light, influence of, 29, 30, 37. 
Lillie, 26, 56. 
Limnsea, 104. 
Linckia multiformis, 102. 
Lithium salts, 286. 
Liver, in, 180. 
Liverworts, 16. 
Lizard, 6, 94, 106; double tail, 137-139; 198, 

214, 290. 
Lobster, 153. 
Locb, J., 24, 29, 30, 31, 33, 34, 35, 42, 59, 

67, 68, 102, 114, 131, 139^ 141, 189,231, 
267, 268. 

Loeb, Leo, 179. 

Ludwig, 105. 

Lumbricus rubellus, 172, 174, 175. 

Lumbriculus, 43, 104« 144^ 149, 190^ 191. 

Lung, 112. 

Lunularia vulgaris, 84, 85. 

Lymphatic glands, 121; grafting upon, 179. 

/Mammals, 97, 11 7-1 18; giufting, 178. 
\Man, 107; grafting, 178, 179. 

Alantis, 100, 104."' 

Margelis carolinensis, 34. 

Marshall, 124-125. 

Martens, von, 102. 

Mauritius, fighting cocks, 97, io6w 

Mechanism, 277. 

Meckel, 208. 

Mesoderm, 193, 194. 

Metridium, 104. 

Michel, 190, 192. 

Minchin, 105. 

Minimal size, 55-57. 

Molgula manhattensis, 237. 

Mollusks, 104. 

Morgan, 9, 30, 32, 33, 43, 44, 57-62, 64, 65, 

68, 126, 131, 175, 185, 186, 187, 225, 231, 
232, 237, 238, 243, 246, 247, 248, 249, 
268. 

Morphallaxis, 13, 270-271. 
Mosses, 16, 17. 
Moulds, 16. 
Mouse, 178. 

Digitized by LjOOQIC 



314 Wdex 



Mucor mucedo, 86. 

Muller» E., 112. 

MuUcr, Fritz, lOO, 213. 

Mus decumanus, 178. 

Mus sylvaticus, 178. 

Muscles, 114, 116, 120, 128, 181. 

Myriapods, 100, 104; autotomy, 154. 

Nageli, 278, 280. 

Nais, 104, 146. 

Natural selection, 96, io8~1 10, 155-1571 262, 

290, 292. 
Necturus, 106. 
Nematodes, 104. 
Nemerteaiis, 104, 143. 
Nereis, 143. 
Nerves, 114. 
Nervous system, 1 14. 
Newport, 100, 154. 
Nothnagel, 116, 117, 120. 
Nucleus, influence of, 66, 67, 258, 281. 
Nussbaum, 20, 66, 202, 203. 

Oblique surface, 44-52, 281. 

Oka, 210. 

Old part, influence of, 62-65. 

Oligochaeta, 143. 

Ontogeny, 212-215, ^^2. 

Organization, 251, 275, 277, 278, 279, 288. 

" Origin of Species," 109. 

Ovary, 124. 

Oxygen, influence of, 36, 77-78. 

Palla, 66. 

Palolo, 143. 

Paramoecium, 103. 

Parypha, see Tubularia. 

Pathological Regeneration, 21. 

Peebles, F., hydra, 27, 56, 63, loi, 167, 168. 

Peipers, 113. 

Pekelharing, 118. 

Pennaria tiarella, 35. 

Petromyzon, 105. 

Pfliiger, 216, 242-243, 246, 252, 256, 264, 265, 

288. 
Phagocata, 104. 
Phallusia mammalata, 236. 
Phasmids, 154. 
Phialidium variabile, 142. 
Phillipeaux, 112, 200. 
Phoxichilidium maxillare, 102. 
Phylogeny, 21 2-21 5. 
Physa, 104. 

Physiological Regeneration, 19, 25, 1 28-131. 
Pizon, 210. 



Planaria lugubris, see Planarian. 

Planaria maculata, see Planarian. 

Planaria torva, 26. 

Planarian, 9, 11, 13, 27, 28, 29, 40, 41, 43. 
44-51, 64-65, 104, 107, 129. I33-I35» 
136, 141, 142, 201, 207, 273, 28a 

Planorbis, 104. 

Plants, 15, 70-91. 

Plasomes, 278. 

Platodes, X04. 

Plethedon cinereus, 201. 

Pliny, I. 

Podocoryne, 103, 168. 

Podwyssozki, 113. 

Poisons, 123. 

Polarity, 38-4D, 43. I77. «77. 280. 

Polychseta, 143. 

Polyclads, 104. 

Polyzoa, 149. 

Ponfick, III. 

Populus dilatata, 75, 76, 80. 

Post-generation, 20; criticism of, 20 (foot- 
note) ; 216, 219-221. 

Pringsheim, 17, 86. 

Proglottids, 146. 

Proteus, 106. 

Protozoa, 103, 145. 

Przibram, 63, 100, 213, 

Purpose, 282, 283. 

Qualitative division of nucleus, 263. 

Rabbit, 112, 113, 117, 1 18, 179. 

Rana esculenta, 184. 

Rana palustris, 185. 

Rana virescens, 185. 

Rand, 124, 164. 

Randolph, 136, 190, 194. 

Rat, 113, 179. 

Rathburn, 153. 

Rauber, 263-264. 

Reaumur, i; experiments with worm and 
with hydra, 2; 92, 151. 

Recklinghausen, 118. 

Regeneration, definition of, 19-25; incom- 
plete, 125. 

Regular Regeneration, 25. 

Regulation, 22. 

Remak, 208. 

Reparation, 22. 

Restitution, 22. 

Restorative Regeneration, 25. 

Rhabdocnelous, Planarians, 142, 149. 

Ribbert, 112, 115, 117, 1 79-181. 

Rievel, 190. 






1 



1 



Digitized by LjOOQ IC 



INDEX 



315 



Roots, 80. 
Rothig, 112. 

Roux, definition of Regeneration, 20, 22, 183, 
216-226, 243, 250, 252, 256, 288. 

Sachs, 81, 88, 89; theory of Regeneration, 
265-267. 

Salamander, 5, 6, 11, 43, 200, 213, 214, 270. 

Salamandra maculata, 205. 

Salensky, 210. 

Salivary gland, 112, 113, l8a 

Salix viminalis, 77. 

Samuel, 1 1 8. 

Sarasin, 102. 

Sars, 102. 

Schaper, 182. 

Schmidt, O., 103. 

Schmitz, 65. 

Schostokowitsch, 85. 

Schreiber, 106. 

Schuberg, 129. 

Schultz, 100, loi, 102, 154.. 

Schultze, 139, 225-227. 

Scudder, 100, 154. 

Scutigera forceps, 154. 

Scyphistoma, 104, 142, 149. 

Scyphozoa, 104. 

Sea-urchin, 18, 19, 105. 

Sea-urchin's egg, 228. 

Seeliger, 68, 210. 

Self-division, 142. 

Self-regulation, 22. 

Semper, 93, 190. 

Sertoli's cells, 181. 

Sharks, 105. 

Siredon, 199. 

Skin, 178, 179, 180. 

Snail, 213. 

Snakes, 106. 

Spallanzani, Prodromo, i, 4; experiments 
with earthworms, 4; tadpole, 5; salaman- 
ders, 5 ; snail, 5, 26, 38, 104, 153, 182, 200. 

Spemann, 227. 

Spencer, Herbert, 263. 

Sphserechinus granularis, 68. 

Spiders, 100, 104. 

Spina bifida, 6. 

Spleen, 124. 

Sponges, 103, 142, 143, 149. 

Spur of cock, 178. 

Starfish, 18, 19, 102, 103, 105, no, 144* 153, 
214, 284. 

Stenopus chrysops, 133, 274, 281. 

Stentor, 14, 15, 56, 66, 67, 103, 129. 

Stimulus, 283, 284, 285. 



Stomobranchium mirabile, 142. 

Stork, 97. 

Strassen, zur, 189. 

Strieker, 119. 

Stuffs, 265-269. 

Syllids, 143. 

Syllis ramosa, 149. 

Tadpole, 1 1, 45 ; closing of wound, 70; 106, 

137, 182-186, 197, 199-200. 
Tail, 197. 
Tapeworm, 143. 
Tarantula, 100, 154. 
Teleology, 282, 288-292. 
Teleost's egg, 237. 
Temperature, 26-27, 37. 
Tension, 272-278; in egg, 274. 
Testes, 117, 124, 181. 
Tetrastemma, 104. 
Thallasicolla nucleata, 67. 
Theories of Regeneration, 26a 
Tornier, 54, 137, 139, 214. 
Tower, 203. 
Towle, 97, 201. 
Townsend, 66. 
Trachea, 180. 
Transplantation, 179. 
Trematodes, 104. 
Trembley, 1 ; experiments with hydra, 2, 20, 

26, 38, 43, 159, 202. 
Triclads, 104. 
Triton cristatus, 137. 
Triton eye, 112; lens, 112. 
Triton marmoratus, 106. 
Tubifex, 104, 191. 
Tubularia, 25, 33, 34, 52, 56-62, 69, 70, 

103, 129, 167-168,267,273. 
Turtles, 106. 

Urodeles, 106, 197. 

Valle, della, 210. 

Vernon, 68. 

Vertebne, 181. 

Ver^'orn, 66, 67. 

Virchow, 115. 

Vitalism, 277, 284, 285. 

Vochting, 16, 57, 71-91, 131, 176, 269. 

Vries, de, 278. 

Vulpian, 182. 

Wagner, von, 144, 149, 190, 192. 
Wagner, W,, lOO. 
Walter, 221. 
Wax glands, 180. 



Digitized by LjOOQIC 



3i6 



INDEX 



Weigert, Ii8, 119. 

Weisman, 93-96, 97, loi, 106, io8» 1 1 2, 

129-130, 245, 252, 256, 261-263, 278. 
Wetzel, 159, 169, 227. 
White ants, 154. 
Whitmann, 280. 

Whole embryos, of reduced size, 222. 
Wiesner, 278. 
Willow, 71-82. 



Wilson, E. B., 68, 139, 231, 237, 250, 251, 

256. 
WolH, C. F., 207, 208. 
Wolff, G., 112, 203, 205, 206, 291, 292. 

Zahn, 124, 178. 

Ziegler, 115, 1 18, 1 19, 121, 240-241, 243, 

246* 
Zoja, 237. 



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\ 



l,/-^ 



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Digitized by VjOOQIC